Patrick John Casey

Journal Article Breast Cancer Res · July 4, 2024 GNA13 (Gα13) is one of two alpha subunit members of the G12/13 family of heterotrimeric G-proteins which mediate signaling downstream of GPCRs. It is known to be essential for embryonic development and vasculogenesis and has been increasingly shown to be i ... Full text Link to item Cite

GPCR-Gα13 Involvement in Mitochondrial Function, Oxidative Stress, and Prostate Cancer.

Journal Article Int J Mol Sci · June 28, 2024 Gα13 and Gα12, encoded by the GNA13 and GNA12 genes, respectively, are members of the G12 family of Gα proteins that, along with their associated Gβγ subunits, mediate signaling from specific G protein-coupled receptors (GPCRs). Advanced prostate cancers h ... Full text Link to item Cite

RAB4A GTPase regulates epithelial-to-mesenchymal transition by modulating RAC1 activation.

Journal Article Breast Cancer Res · October 28, 2022 Epithelial-to-mesenchymal transition (EMT) is a critical underpinning process for cancer progression, recurrence and resistance to drug treatment. Identification of new regulators of EMT could lead to the development of effective therapies to improve the o ... Full text Link to item Cite

The emerging roles of Gα12/13 proteins on the hallmarks of cancer in solid tumors.

Journal Article Oncogene · January 2022 G12 proteins comprise a subfamily of G-alpha subunits of heterotrimeric GTP-binding proteins (G proteins) that link specific cell surface G protein-coupled receptors (GPCRs) to downstream signaling molecules and play important roles in human physiology. Th ... Full text Link to item Cite

Suppression of isoprenylcysteine carboxylmethyltransferase compromises DNA damage repair.

Journal Article Life Sci Alliance · December 2021 DNA damage is a double-edged sword for cancer cells. On the one hand, DNA damage-induced genomic instability contributes to cancer development; on the other hand, accumulating damage compromises proliferation and survival of cancer cells. Understanding the ... Full text Link to item Cite

Evaluating the Epithelial-Mesenchymal Program in Human Breast Epithelial Cells Cultured in Soft Agar Using a Novel Macromolecule Extraction Protocol.

Journal Article Cancers (Basel) · February 15, 2021 The ability to grow in anchorage-independent conditions is an important feature of malignant cells, and it is well-established that cellular phenotypes in adherent cultures can differ widely from phenotypes observed in xenografts and anchorage-independent ... Full text Link to item Cite

Isoprenylcysteine carboxylmethyltransferase is required for the impact of mutant KRAS on TAZ protein level and cancer cell self-renewal.

Journal Article Oncogene · July 2020 Cancer stem cells possess the capacity for self-renewal and resistance to chemotherapy. It is therefore crucial to understand the molecular regulators of stemness in the quest to develop effective cancer therapies. TAZ is a transcription activator that pro ... Full text Link to item Cite

Gα-13 induces CXC motif chemokine ligand 5 expression in prostate cancer cells by transactivating NF-κB.

Journal Article J Biol Chem · November 29, 2019 GNA13, the α subunit of a heterotrimeric G protein, mediates signaling through G-protein-coupled receptors (GPCRs). GNA13 is up-regulated in many solid tumors, including prostate cancer, where it contributes to tumor initiation, drug resistance, and metast ... Full text Link to item Cite

p21cip1/waf1 Coordinate Autophagy, Proliferation and Apoptosis in Response to Metabolic Stress.

Journal Article Cancers (Basel) · August 3, 2019 Cancer cells possess metabolic properties that are different from benign cells. These unique characteristics have become attractive targets that are being actively investigated for cancer therapy. p21cip1/waf1, also known as Cyclin-Dependent Kinase inhibit ... Full text Link to item Cite

Respiratory Capacity and Reserve Predict Cell Sensitivity to Mitochondria Inhibitors: Mechanism-Based Markers to Identify Metformin-Responsive Cancers.

Journal Article Mol Cancer Ther · March 2019 Metformin has been extensively studied for its impact on cancer cell metabolism and anticancer potential. Despite evidence of significant reduction in cancer occurrence in diabetic patients taking metformin, phase II cancer trials of the agent have been di ... Full text Link to item Cite

GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers.

Journal Article Oncogene · March 2018 Treatment failure in solid tumors occurs due to the survival of specific subpopulations of cells that possess tumor-initiating (TIC) phenotypes. Studies have implicated G protein-coupled-receptors (GPCRs) in cancer progression and the acquisition of TIC ph ... Full text Link to item Cite

Isoprenylcysteine carboxylmethyltransferase function is essential for RAB4A-mediated integrin β3 recycling, cell migration and cancer metastasis.

Journal Article Oncogene · October 12, 2017 Isoprenylcysteine carboxylmethyltransferase (ICMT) catalyzes the post-translational modification of RAB GTPases that contain C-terminal CXC motifs. However, the functional impact of this modification on RAB proteins has not been actively explored. We found ... Full text Link to item Cite

Isoprenylcysteine carboxylmethyltransferase is critical for malignant transformation and tumor maintenance by all RAS isoforms.

Journal Article Oncogene · July 6, 2017 Despite extensive effort, there has been limited progress in the development of direct RAS inhibitors. Targeting isoprenylcysteine carboxylmethyltransferase (ICMT), a unique enzyme of RAS post-translational modification, represents a promising strategy to ... Full text Link to item Cite

Inhibition of Isoprenylcysteine Carboxylmethyltransferase Induces Cell-Cycle Arrest and Apoptosis through p21 and p21-Regulated BNIP3 Induction in Pancreatic Cancer.

Journal Article Mol Cancer Ther · May 2017 Pancreatic cancer remains one of the most difficult to treat human cancers despite recent advances in targeted therapy. Inhibition of isoprenylcysteine carboxylmethyltransferase (ICMT), an enzyme that posttranslationally modifies a group of proteins includ ... Full text Link to item Cite

c-Jun Contributes to Transcriptional Control of GNA12 Expression in Prostate Cancer Cells.

Journal Article Molecules · April 10, 2017 Abstract: GNA12 is the α subunit of a heterotrimeric G protein that possesses oncogenic potential. Activated GNA12 also promotes prostate and breast cancer cell invasion in vitro and in vivo, and its expression is up-regulated in many tumors, particularly ... Full text Link to item Cite

Activation of MAPK/ERK signaling by Burkholderia pseudomallei cycle inhibiting factor (Cif).

Journal Article PLoS One · 2017 Cycle inhibiting factors (Cifs) are virulence proteins secreted by the type III secretion system of some Gram-negative pathogenic bacteria including Burkholderia pseudomallei. Cif is known to function to deamidate Nedd8, leading to inhibition of Cullin E3 ... Full text Link to item Cite

The GNA13-RhoA signaling axis suppresses expression of tumor protective Kallikreins.

Journal Article Cell Signal · October 2016 Gα13 (encoded by GNA13 gene) is the alpha subunit of a heterotrimeric G-protein that mediates signaling through specific G-protein-coupled receptors (GPCRs). Increased GNA13 expression has been observed in metastatic breast cancer cells. Recently, we have ... Full text Link to item Cite

GNA13 loss in germinal center B cells leads to impaired apoptosis and promotes lymphoma in vivo.

Journal Article Blood · June 2, 2016 GNA13 is the most frequently mutated gene in germinal center (GC)-derived B-cell lymphomas, including nearly a quarter of Burkitt lymphoma and GC-derived diffuse large B-cell lymphoma. These mutations occur in a pattern consistent with loss of function. We ... Full text Link to item Cite

Inhibition of isoprenylcysteine carboxylmethyltransferase augments BCR-ABL1 tyrosine kinase inhibition-induced apoptosis in chronic myeloid leukemia.

Journal Article Exp Hematol · March 2016 Despite the success of BCR-ABL1 tyrosine kinase inhibitors in patients with chronic myeloid leukemia (CML), resistance to tyrosine kinase inhibitors remains a therapeutic challenge. One strategy used to overcome resistance is combination of existing BCR-AB ... Full text Link to item Cite

Protein prenylation: unique fats make their mark on biology.

Journal Article Nat Rev Mol Cell Biol · February 2016 The modification of eukaryotic proteins by isoprenoid lipids, which is known as prenylation, controls the localization and activity of a range of proteins that have crucial functions in biological regulation. The roles of prenylated proteins in cells are w ... Full text Link to item Cite

GNA13 suppresses proliferation of ER+ breast cancer cells via ERα dependent upregulation of the MYC oncogene.

GPCR-Gα13 Involvement in Mitochondrial Function, Oxidative Stress, and Prostate Cancer.

RAB4A GTPase regulates epithelial-to-mesenchymal transition by modulating RAC1 activation.

The emerging roles of Gα12/13 proteins on the hallmarks of cancer in solid tumors.

Suppression of isoprenylcysteine carboxylmethyltransferase compromises DNA damage repair.

Evaluating the Epithelial-Mesenchymal Program in Human Breast Epithelial Cells Cultured in Soft Agar Using a Novel Macromolecule Extraction Protocol.

Isoprenylcysteine carboxylmethyltransferase is required for the impact of mutant KRAS on TAZ protein level and cancer cell self-renewal.

Gα-13 induces CXC motif chemokine ligand 5 expression in prostate cancer cells by transactivating NF-κB.

p21cip1/waf1 Coordinate Autophagy, Proliferation and Apoptosis in Response to Metabolic Stress.

Respiratory Capacity and Reserve Predict Cell Sensitivity to Mitochondria Inhibitors: Mechanism-Based Markers to Identify Metformin-Responsive Cancers.

GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers.

Isoprenylcysteine carboxylmethyltransferase function is essential for RAB4A-mediated integrin β3 recycling, cell migration and cancer metastasis.

Isoprenylcysteine carboxylmethyltransferase is critical for malignant transformation and tumor maintenance by all RAS isoforms.

Inhibition of Isoprenylcysteine Carboxylmethyltransferase Induces Cell-Cycle Arrest and Apoptosis through p21 and p21-Regulated BNIP3 Induction in Pancreatic Cancer.

c-Jun Contributes to Transcriptional Control of GNA12 Expression in Prostate Cancer Cells.

Activation of MAPK/ERK signaling by Burkholderia pseudomallei cycle inhibiting factor (Cif).

The GNA13-RhoA signaling axis suppresses expression of tumor protective Kallikreins.

GNA13 loss in germinal center B cells leads to impaired apoptosis and promotes lymphoma in vivo.

Inhibition of isoprenylcysteine carboxylmethyltransferase augments BCR-ABL1 tyrosine kinase inhibition-induced apoptosis in chronic myeloid leukemia.

Protein prenylation: unique fats make their mark on biology.

Protein Geranylgeranyltransferase Type 1 as a Target in Cancer.

Journal Article Curr Cancer Drug Targets · 2016 The process of protein prenylation involves the covalent linkage of either farnesyl (15-carbon) or geranylgeranyl (20-carbon) isoprenoid lipds to conserved cysteine residues in the carboxyl-terminus of proteins. Protein geranylgeranyltransferase I (GGTase- ... Full text Link to item Cite

Isoprenylcysteine carboxylmethyltransferase regulates mitochondrial respiration and cancer cell metabolism.

Journal Article Oncogene · June 2015 Isoprenylcysteine carboxylmethyltransferase (Icmt) catalyzes the last of the three-step posttranslational protein prenylation process for the so-called CaaX proteins, which includes many signaling proteins, such as most small GTPases. Despite extensive stu ... Full text Link to item Cite

MicroRNA-31 controls G protein alpha-13 (GNA13) expression and cell invasion in breast cancer cells.

Journal Article Mol Cancer · March 26, 2015 BACKGROUND: Gα13 (GNA13) is the α subunit of a heterotrimeric G protein that mediates signaling through specific G protein-coupled receptors (GPCRs). Our recent study showed that control of GNA13 expression by specific microRNAs (miRNAs or miRs) is importa ... Full text Link to item Cite

An improved isoprenylcysteine carboxylmethyltransferase inhibitor induces cancer cell death and attenuates tumor growth in vivo.

Journal Article Cancer Biol Ther · September 2014 Inhibitors of isoprenylcysteine carboxylmethyltransferase (Icmt) are promising anti-cancer agents, as modification by Icmt is an essential component of the protein prenylation pathway for a group of proteins that includes Ras GTPases. Cysmethynil, a protot ... Full text Link to item Cite

Inhibitory G proteins and their receptors: emerging therapeutic targets for obesity and diabetes.

Journal Article Exp Mol Med · June 20, 2014 The worldwide prevalence of obesity is steadily increasing, nearly doubling between 1980 and 2008. Obesity is often associated with insulin resistance, a major risk factor for type 2 diabetes mellitus (T2DM): a costly chronic disease and serious public hea ... Full text Link to item Cite

Gαz regulates BDNF-induction of axon growth in cortical neurons.

Journal Article Mol Cell Neurosci · January 2014 The disruption of neurotransmitter and neurotrophic factor signaling in the central nervous system (CNS) is implicated as the root cause of neuropsychiatric disorders, including schizophrenia, epilepsy, chronic pain, and depression. Therefore, identifying ... Full text Link to item Cite

Breast cancer cell invasion mediated by Gα12 signaling involves expression of interleukins-6 and -8, and matrix metalloproteinase-2.

Journal Article J Mol Signal · 2014 BACKGROUND: Recent studies on the involvement of the G12 family of heterotrimeric G proteins (Gα12 and Gα13, the products of the GNA12 and GNA13 genes, respectively) in oncogenic pathways have uncovered a link between G12 signaling and cancer progression. ... Full text Link to item Cite

Control of RhoA methylation by carboxylesterase I.

Journal Article J Biol Chem · June 28, 2013 A number of proteins that play key roles in cell signaling are post-translationally modified by the prenylation pathway. The final step in this pathway is methylation of the carboxyl terminus of the prenylated protein by isoprenylcysteine carboxylmethyltra ... Full text Link to item Cite

Functionalized indoleamines as potent, drug-like inhibitors of isoprenylcysteine carboxyl methyltransferase (Icmt).

Journal Article Eur J Med Chem · May 2013 The enzyme isoprenylcysteine carboxyl methyltransferase (Icmt) plays an important role in the post-translational modification of proteins involved in the regulation of cell growth and oncogenesis. The biological consequences of Icmt inhibition strongly imp ... Full text Link to item Cite

Deciphering the signaling networks underlying simvastatin-induced apoptosis in human cancer cells: evidence for non-canonical activation of RhoA and Rac1 GTPases.

Journal Article Cell Death Dis · April 4, 2013 Although statins are known to inhibit proliferation and induce death in a number of cancer cell types, the mechanisms through which downregulation of the mevalonate (MVA) pathway activates death signaling remain poorly understood. Here we set out to unrave ... Full text Link to item Cite

Deciphering the signaling networks underlying simvastatin-induced apoptosis in human cancer cells: Evidence for non-canonical activation of RhoA and Rac1 GTPases

Journal Article Cell Death and Disease · April 1, 2013 Although statins are known to inhibit proliferation and induce death in a number of cancer cell types, the mechanisms through which downregulation of the mevalonate (MVA) pathway activates death signaling remain poorly understood. Here we set out to unrave ... Full text Cite

MicroRNA-182 and microRNA-200a control G-protein subunit α-13 (GNA13) expression and cell invasion synergistically in prostate cancer cells.

Journal Article J Biol Chem · March 15, 2013 G protein-coupled receptors (GPCRs) and their ligands have been implicated in progression and metastasis of several cancers. GPCRs signal through heterotrimeric G proteins, and among the different types of G proteins, GNA12/13 have been most closely linked ... Full text Link to item Cite

Deletion of GαZ protein protects against diet-induced glucose intolerance via expansion of β-cell mass.

Journal Article J Biol Chem · June 8, 2012 Insufficient plasma insulin levels caused by deficits in both pancreatic β-cell function and mass contribute to the pathogenesis of type 2 diabetes. This loss of insulin-producing capacity is termed β-cell decompensation. Our work is focused on defining th ... Full text Link to item Cite

A role for Rac3 GTPase in the regulation of autophagy.

Journal Article J Biol Chem · October 7, 2011 The process of autophagy is situated at the intersection of multiple cell signaling pathways, including cell metabolism, growth, and death, and hence is subject to multiple forms of regulation. We previously reported that inhibition of isoprenylcysteine ca ... Full text Link to item Cite

Prenylated c17orf37 induces filopodia formation to promote cell migration and metastasis.

Journal Article J Biol Chem · July 22, 2011 Post-translational modification by covalent attachment of isoprenoid lipids (prenylation) regulates the functions and biological activities of several proteins implicated in the oncogenic transformation and metastatic progression of cancer. The largest gro ... Full text Link to item Cite

Site-specific analysis of protein S-acylation by resin-assisted capture.

Journal Article J Lipid Res · February 2011 Protein S-acylation is a major posttranslational modification whereby a cysteine thiol is converted to a thioester. A prototype is S-palmitoylation (fatty acylation), in which a protein undergoes acylation with a hydrophobic 16 carbon lipid chain. Although ... Full text Link to item Cite

G12 signaling through c-Jun NH2-terminal kinase promotes breast cancer cell invasion.

Journal Article PLoS One · 2011 Signaling through the heterotrimeric G protein, G12, via Rho induces a striking increase in breast cancer cell invasion. In this study, evidence is provided that the c-Jun NH(2)-terminal kinase (JNK) is a key downstream effector of G12 on this pathway. Exp ... Full text Link to item Cite

RHO methylation matters: a role for isoprenylcysteine carboxylmethyltransferase in cell migration and adhesion.

Journal Article Cell Adh Migr · 2011 Numerous proteins involved in diverse aspects of cell biology undergo a process of post-translational modification termed prenylation. The prenylation pathway consists of three enzymatic steps, the final of which is methylation of the carboxyl-terminal pre ... Full text Link to item Cite

The Enzymology of CAAX Protein Prenylation

Journal Article · January 1, 2011 Many proteins involved in signal transduction and protein trafficking are posttranslationally modified by the covalent attachment of lipid groups. One form of lipid modification involves attachment of either a 15-carbon farnesyl or a 20-carbon geranylgeran ... Full text Cite

Amino derivatives of indole as potent inhibitors of isoprenylcysteine carboxyl methyltransferase.

Journal Article J Med Chem · October 14, 2010 The enzyme isoprenylcysteine carboxyl methyltransferase (Icmt) plays an important role in the post-translational modification of proteins that are involved in the regulation of cell growth. The indole acetamide cysmethynil is by far the most potent and wid ... Full text Link to item Cite

Inhibition of isoprenylcysteine carboxylmethyltransferase induces autophagic-dependent apoptosis and impairs tumor growth.

Journal Article Oncogene · September 2, 2010 Inhibition of isoprenylcysteine carboxylmethyltransferase (Icmt), which catalyzes the final step in the post-translational C-terminal processing of prenylated proteins, suppresses tumor cell growth and induces cell death. Icmt inhibition by either a small ... Full text Link to item Cite

A prenylated p47phox-p67phox-Rac1 chimera is a Quintessential NADPH oxidase activator: membrane association and functional capacity.

Journal Article J Biol Chem · August 13, 2010 The superoxide-generating NADPH oxidase complex of resting phagocytes includes cytochrome b(559), a membrane-associated heterodimer composed of two subunits (Nox2 and p22(phox)), and four cytosolic proteins (p47(phox), p67(phox), Rac, and p40(phox)). Upon ... Full text Link to item Cite

Rap1 promotes multiple pancreatic islet cell functions and signals through mammalian target of rapamycin complex 1 to enhance proliferation.

Journal Article J Biol Chem · May 21, 2010 Recent studies have implicated Epac2, a guanine-nucleotide exchange factor for the Rap subfamily of monomeric G proteins, as an important regulator of insulin secretion from pancreatic beta-cells. Although the Epac proteins were originally identified as cA ... Full text Link to item Cite

Pharmacological targeting of the mitochondrial phosphatase PTPMT1.

Journal Article J Pharmacol Exp Ther · May 2010 The dual-specificity protein tyrosine phosphatases (PTPs) play integral roles in the regulation of cell signaling. There is a need for new tools to study these phosphatases, and the identification of inhibitors potentially affords not only new means for th ... Full text Link to item Cite

Signaling through G_z

Journal Article Handbook of Cell Signaling, 2/e · 2010 Several studies have been carried out to pinpoint specific brain regions and developmental stages where Gz is transcribed or expressed. The limited tissue distribution of Gαz, its unusual biochemical properties, the identification of Gαz-specific effectors ... Full text Cite

Rho GTPase activity modulates Wnt3a/beta-catenin signaling.

Journal Article Cell Signal · November 2009 Wnt proteins constitute a family of secreted signaling molecules that regulate highly conserved pathways essential for development and, when aberrantly activated, drive oncogenesis in a number of human cancers. A key feature of the most widely studied Wnt ... Full text Link to item Cite

Role of isoprenylcysteine carboxylmethyltransferase-catalyzed methylation in Rho function and migration.

Journal Article J Biol Chem · October 9, 2009 A number of proteins that play key roles in biological regulatory events undergo a process of post-translational modifications termed prenylation. The prenylation pathway consists of three enzymatic steps; the final processed protein is isoprenoid-modified ... Full text Link to item Cite

Role of G12 proteins in oncogenesis and metastasis.

Journal Article Br J Pharmacol · September 2009 The G12 subfamily of heterotrimeric guanine nucleotide-binding proteins consists of two alpha subunits, G alpha12 and G alpha13. These proteins mediate signalling via G protein-coupled receptors and have been implicated in various physiological and pathoph ... Full text Link to item Cite

Discovery of geranylgeranyltransferase-I inhibitors with novel scaffolds by the means of quantitative structure-activity relationship modeling, virtual screening, and experimental validation.

Journal Article J Med Chem · July 23, 2009 Geranylgeranylation is critical to the function of several proteins including Rho, Rap1, Rac, Cdc42, and G-protein gamma subunits. Geranylgeranyltransferase type I (GGTase-I) inhibitors (GGTIs) have therapeutic potential to treat inflammation, multiple scl ... Full text Link to item Cite

Activation of Rap1 promotes prostate cancer metastasis.

Journal Article Cancer Res · June 15, 2009 Elucidating the mechanisms of prostate cancer (CaP) survival and metastasis are critical to the discovery of novel therapeutic targets. The monomeric G protein Rap1 has been implicated in cancer tumorigenesis. Rap1 signals to pathways involved in cell adhe ... Full text Link to item Cite

Topology of mammalian isoprenylcysteine carboxyl methyltransferase determined in live cells with a fluorescent probe.

Journal Article Mol Cell Biol · April 2009 Isoprenylcysteine carboxyl methyltransferase (Icmt) is a highly conserved enzyme that methyl esterifies the alpha carboxyl group of prenylated proteins including Ras and related GTPases. Methyl esterification neutralizes the negative charge of the prenylcy ... Full text Link to item Cite

A high-performance liquid chromatography method for the quantification of cysmethynil, an inhibitor of isoprenylcysteine carboxylmethyl transferase, in mouse plasma.

Journal Article J Chromatogr B Analyt Technol Biomed Life Sci · February 15, 2009 Cysmethynil, a newly identified small molecule inhibitor of isoprenylcysteine carboxylmethyl transferase (Icmt) is involved in the post-translational modification of CaaX proteins. Cysmethynil causes cell death in many human cancer cells in vitro, and inhi ... Full text Link to item Cite

Signaling Through Gz

Chapter · January 1, 2009 Several studies have been carried out to pinpoint specific brain regions and developmental stages where Gz is transcribed or expressed. The limited tissue distribution of Gαz, its unusual biochemical properties, the identification of Gαz-specific effectors ... Full text Cite

Interacting targets of the farnesyl of transducin gamma-subunit.

Journal Article Biochemistry · August 12, 2008 G protein gamma-subunits are isoprenylated and carboxyl methylated at the C-terminal cysteine residue, and the set of the posttranslational modifications is indispensable for the function of the photoreceptor G protein transducin (Talpha/Tbetagamma). To ex ... Full text Link to item Cite

A small molecule inhibitor of isoprenylcysteine carboxymethyltransferase induces autophagic cell death in PC3 prostate cancer cells.

Journal Article J Biol Chem · July 4, 2008 A number of proteins involved in cell growth control, including members of the Ras family of GTPases, are modified at their C terminus by a three-step posttranslational process termed prenylation. The enzyme isoprenylcysteine carboxylmethyl-transferase (Ic ... Full text Link to item Cite

Effects of pharmacologic inhibition of protein geranylgeranyltransferase type I on aqueous humor outflow through the trabecular meshwork.

Journal Article Invest Ophthalmol Vis Sci · June 2008 PURPOSE: To determine the effects of inhibition of protein geranylgeranyltransferase type I (GGTase-I), which isoprenylates so-called CaaX proteins, including the GTP-binding proteins such as Rho GTPases and the betagamma subunits of heterotrimeric G-prote ... Full text Link to item Cite

Galphaz negatively regulates insulin secretion and glucose clearance.

Journal Article J Biol Chem · February 22, 2008 Relatively little is known about the in vivo functions of the alpha subunit of the heterotrimeric G protein Gz (Galphaz). Clues to one potential function recently emerged with the finding that activation of Galphaz inhibits glucose-stimulated insulin secre ... Full text Link to item Cite

A global partnership in medical education between Duke University and the National University of Singapore.

Journal Article Acad Med · February 2008 Duke University and the National University of Singapore (NUS) have partnered to launch a new medical school that brings the American style of postbaccalaureate medical education to Asia. The new institution, called the Duke-NUS Graduate Medical School (GM ... Full text Link to item Cite

beta-Catenin is a Nek2 substrate involved in centrosome separation.

Journal Article Genes Dev · January 1, 2008 beta-Catenin plays important roles in cell adhesion and gene transcription, and has been shown recently to be essential for the establishment of a bipolar mitotic spindle. Here we show that beta-catenin is a component of interphase centrosomes and that sta ... Full text Link to item Cite

Biologic functions of the G12 subfamily of heterotrimeric g proteins: growth, migration, and metastasis.

Journal Article Biochemistry · June 12, 2007 The G12 subfamily of heterotrimeric G proteins has been the subject of intense scientific interest for more than 15 years. During this period, studies have revealed more than 20 potential G12-interacting proteins and numerous signaling axes emanating from ... Full text Link to item Cite

GGTase-I deficiency reduces tumor formation and improves survival in mice with K-RAS-induced lung cancer.

Journal Article J Clin Invest · May 2007 Protein geranylgeranyltransferase type I (GGTase-I) is responsible for the posttranslational lipidation of CAAX proteins such as RHOA, RAC1, and cell division cycle 42 (CDC42). Inhibition of GGTase-I has been suggested as a strategy to treat cancer and a h ... Full text Link to item Cite

Quantitative structure-activity relationship (QSAR) of indoloacetamides as inhibitors of human isoprenylcysteine carboxyl methyltransferase.

Journal Article Bioorg Med Chem Lett · February 15, 2007 A QSAR is developed for the isoprenylcysteine carboxyl methyltransferase (ICMT) inhibitory activities of a series of indoloacetamides (n=72) that are structurally related to cysmethynil, a selective ICMT inhibitor. Multivariate analytical tools (principal ... Full text Link to item Cite

Time-dependent inhibition of isoprenylcysteine carboxyl methyltransferase by indole-based small molecules.

Journal Article Biochemistry · January 16, 2007 Isoprenylcysteine carboxyl methyltransferase (Icmt) catalyzes the methylation of the C-terminal prenylcysteine found on prenylated proteins. Numerous studies have shown that the methylation step is important for the correct localization and function of man ... Full text Link to item Cite

The regulator of G protein signaling domain of axin selectively interacts with Galpha12 but not Galpha13.

Journal Article Mol Pharmacol · October 2006 Axin, a negative regulator of the Wnt signaling pathway, contains a canonical regulator of G protein signaling (RGS) core domain. Herein, we demonstrate both in vitro and in cells that this domain interacts with the alpha subunit of the heterotrimeric G pr ... Full text Link to item Cite

A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion.

Journal Article J Biol Chem · September 8, 2006 Many studies have suggested a role for the members of the G12 family of heterotrimeric G proteins (Galpha12 and Galpha13) in oncogenesis and tumor cell growth. However, few studies have examined G12 signaling in actual human cancers. In this study, we exam ... Full text Link to item Cite

Conversion of protein farnesyltransferase to a geranylgeranyltransferase.

Journal Article Biochemistry · August 15, 2006 Posttranslational modifications are essential for the proper function of a number of proteins in the cell. One such modification, the covalent attachment of a single isoprenoid lipid (prenylation), is carried out by the CaaX prenyltransferases, protein far ... Full text Link to item Cite

The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis.

Journal Article Proc Natl Acad Sci U S A · May 23, 2006 Although the prognosis for patients with early-stage breast cancer has improved, the therapeutic options for patients with locally advanced and metastatic disease are limited. To improve the treatment of these patients, the molecular mechanisms underlying ... Full text Link to item Cite

A novel protein geranylgeranyltransferase-I inhibitor with high potency, selectivity, and cellular activity.

Journal Article J Biol Chem · May 5, 2006 Inhibiting protein prenylation is an attractive means to modulate cellular processes controlled by a variety of signaling proteins, including oncogenic proteins such as Ras and Rho GTPases. The largest class of prenylated proteins contain a so-called CaaX ... Full text Link to item Cite

Isoprenylcysteine carboxylmethyltransferase as a target for development of novel cancer therapeutics

Journal Article Drugs of the Future · May 1, 2006 Isoprenylcysteine carboxylmethyltransferase (lcmt), which catalyzes the last step of the three-step post-translational modification of a group of proteins containing the so-called CaaX motif, has become the focus of research in the quest for discovering ne ... Full text Cite

Genetic and pharmacologic analyses of the role of Icmt in Ras membrane association and function.

Journal Article Methods Enzymol · 2006 After isoprenylation, the Ras proteins and other proteins terminating with a so-called CAAX motif undergo two additional modifications: (1) endoproteolytic cleavage of the -AAX by Ras converting enzyme 1 (Rce1) and (2) carboxyl methylation of the isoprenyl ... Full text Link to item Cite

A role for G(z) in pancreatic islet beta-cell biology.

Journal Article J Biol Chem · September 9, 2005 Glucose-stimulated insulin secretion and beta-cell growth are important facets of pancreatic islet beta-cell biology. As a result, factors that modulate these processes are of great interest for the potential treatment of Type 2 diabetes. Here, we present ... Full text Link to item Cite

Involvement of a mitochondrial phosphatase in the regulation of ATP production and insulin secretion in pancreatic beta cells.

Journal Article Mol Cell · July 22, 2005 Reversible phosphorylation is the cell's most prevalent form of posttranslational modification, yet its role in the regulation of mitochondrial functions is poorly understood. We have discovered that a member of the dual-specific protein tyrosine phosphata ... Full text Link to item Cite

Selective uncoupling of G alpha 12 from Rho-mediated signaling.

Journal Article J Biol Chem · May 6, 2005 The heterotrimeric G protein G(12) has been implicated in such cellular regulatory processes as cytoskeletal rearrangement, cell-cell adhesion, and oncogenic transformation. Although the activated alpha-subunit of G(12) has been shown to interact directly ... Full text Link to item Cite

Post-prenylation-processing enzymes as new targets in oncogenesis.

Journal Article Nat Rev Cancer · May 2005 RAS and many other oncogenic proteins undergo a complex series of post-translational modifications that are initiated by the addition of an isoprenoid lipid through a process known as prenylation. Following prenylation, these proteins usually undergo endop ... Full text Link to item Cite

Protein farnesyltransferase in embryogenesis, adult homeostasis, and tumor development.

Journal Article Cancer Cell · April 2005 Protein farnesyltransferase (FTase) is an enzyme responsible for posttranslational modification of proteins carrying a carboxy-terminal CaaX motif. Farnesylation allows substrates to interact with membranes and protein targets. Using gene-targeted mice, we ... Full text Link to item Cite

Rap1 GTPase inhibits leukocyte transmigration by promoting endothelial barrier function.

Journal Article J Biol Chem · March 25, 2005 The passage of leukocytes out of the blood circulation and into tissues is necessary for the normal inflammatory response, but it also occurs inappropriately in many pathological situations. This process is limited by the barrier presented by the junctions ... Full text Link to item Cite

Androgen receptor activation by G(s) signaling in prostate cancer cells.

Journal Article J Biol Chem · March 25, 2005 The androgen receptor (AR) is activated in prostate cancer patients undergoing androgen ablative therapy and mediates growth of androgen-insensitive prostate cancer cells, suggesting it is activated by nonandrogenic factors. We demonstrate that activated a ... Full text Link to item Cite

A small-molecule inhibitor of isoprenylcysteine carboxyl methyltransferase with antitumor activity in cancer cells.

Journal Article Proc Natl Acad Sci U S A · March 22, 2005 Many key regulatory proteins, including members of the Ras family of GTPases, are modified at their C terminus by a process termed prenylation. This processing is initiated by the addition of an isoprenoid lipid, and the proteins are further modified by a ... Full text Link to item Cite

Pertussis-toxin-sensitive Galpha subunits selectively bind to C-terminal domain of neuronal GIRK channels: evidence for a heterotrimeric G-protein-channel complex.

Journal Article Mol Cell Neurosci · February 2005 Neuronal G-protein-gated inwardly rectifying potassium (Kir3; GIRK) channels are activated by G-protein-coupled receptors that selectively interact with PTX-sensitive (Galphai/o) G proteins. Although the Gbetagamma dimer is known to activate GIRK channels, ... Full text Link to item Cite

Analysis of the kinetic mechanism of recombinant human isoprenylcysteine carboxylmethyltransferase (Icmt).

Journal Article BMC Biochem · December 29, 2004 BACKGROUND: Isoprenylcysteine carboxyl methyltransferase (Icmt) is the third of three enzymes that posttranslationally modify proteins that contain C-terminal CaaX motifs. The processing of CaaX proteins through this so-called prenylation pathway via a rou ... Full text Link to item Cite

Reciprocal signaling between the transcriptional co-factor Eya2 and specific members of the Galphai family.

Journal Article Mol Pharmacol · November 2004 As part of a program to elucidate signaling processes controlled by the heterotrimeric G protein Galphaz, a human fetal brain cDNA library was screened for proteins that specifically interact with the activated form of Galphaz. One of the most-encountered ... Full text Link to item Cite

Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity.

Journal Article J Mol Biol · October 15, 2004 Post-translational modifications are essential for the proper function of many proteins in the cell. The attachment of an isoprenoid lipid (a process termed prenylation) by protein farnesyltransferase (FTase) or geranylgeranyltransferase type I (GGTase-I) ... Full text Link to item Cite

Identification of a role for beta-catenin in the establishment of a bipolar mitotic spindle.

Journal Article J Biol Chem · March 19, 2004 beta-Catenin is a multifunctional protein that is known to participate in two well defined cellular processes, cell-cell adhesion and Wnt-stimulated transcriptional activation. Here we report that beta-catenin participates in a third cellular process, the ... Full text Link to item Cite

On the physiological importance of endoproteolysis of CAAX proteins: heart-specific RCE1 knockout mice develop a lethal cardiomyopathy.

Journal Article J Biol Chem · February 6, 2004 Proteins terminating with a CAAX motif, such as the Ras proteins and the nuclear lamins, undergo post-translational modification of a C-terminal cysteine with an isoprenyl lipid via a process called protein prenylation. After prenylation, the last three re ... Full text Link to item Cite

Inactivation of Icmt inhibits transformation by oncogenic K-Ras and B-Raf.

Journal Article J Clin Invest · February 2004 Isoprenylcysteine carboxyl methyltransferase (Icmt) methylates the carboxyl-terminal isoprenylcysteine of CAAX proteins (e.g., Ras and Rho proteins). In the case of the Ras proteins, carboxyl methylation is important for targeting of the proteins to the pl ... Full text Link to item Cite

Analysis of the molecular interaction of the farnesyl moiety of transducin through the use of a photoreactive farnesyl analogue.

Journal Article Biochemistry · January 20, 2004 Farnesylation of the gamma-subunit of the retinal G-protein, transducin (Talpha/Tbetagamma), is indispensable for light-initiated signaling in photoreceptor cells. However, the farnesyl-mediated molecular interactions important for signaling are not well u ... Full text Link to item Cite

Analysis of the regulation of microtubule dynamics by interaction of RGSZ1 (RGS20) with the neuronal stathmin, SCG10.

Journal Article Methods Enzymol · 2004 Regulators of G protein signaling (RGS proteins) are a diverse family of proteins that act to negatively regulate signaling by heterotrimeric G proteins; however, recent data have implied additional functions for RGS proteins. Previously, we employed the y ... Full text Link to item Cite

Improved loading and cleavage methods for solid-phase synthesis using chlorotrityl resins: synthesis and testing of a library of 144 discrete chemicals as potential farnesyltransferase inhibitors.

Journal Article J Comb Chem · 2004 The use of chlorotrityl resins for the immobilization of amines is sometimes deterred by the lengthy process of loading the reactants on the resins and product decomposition caused by the reactive chlorotrityl group in the presence of 1% TFA as a cleavage ... Full text Link to item Cite

Structure of mammalian protein geranylgeranyltransferase type-I.

Journal Article EMBO J · November 17, 2003 Featured Publication Protein geranylgeranyltransferase type-I (GGTase-I), one of two CaaX prenyltransferases, is an essential enzyme in eukaryotes. GGTase-I catalyzes C-terminal lipidation of >100 proteins, including many GTP- binding regulatory proteins. We present the first ... Full text Link to item Cite

High affinity for farnesyltransferase and alternative prenylation contribute individually to K-Ras4B resistance to farnesyltransferase inhibitors.

Journal Article J Biol Chem · October 24, 2003 Farnesyltransferase inhibitors (FTIs) block Ras farnesylation, subcellular localization and activity, and inhibit the growth of Ras-transformed cells. Although FTIs are ineffective against K-Ras4B, the Ras isoform most commonly mutated in human cancers, th ... Full text Link to item Cite

Kinetic studies of protein farnesyltransferase mutants establish active substrate conformation.

Journal Article Biochemistry · August 19, 2003 The zinc metalloenzyme protein farnesyltransferase (FTase) catalyzes the transfer of a 15-carbon farnesyl moiety from farnesyl diphosphate (FPP) to a cysteine residue near the C-terminus of a protein substrate. Several crystal structures of inactive FTase. ... Full text Link to item Cite

Targeting Ras signaling through inhibition of carboxyl methylation: an unexpected property of methotrexate.

Journal Article Proc Natl Acad Sci U S A · May 27, 2003 Featured Publication The antifolate methotrexate is one of the most successful drugs in cancer chemotherapy. Although its efficacy is widely attributed to a decrease in nucleotide biosynthesis (1), methotrexate is known to increase homocysteine (2), a compound associated with ... Full text Link to item Cite

Signaling through Gz

Chapter · January 1, 2003 Full text Cite

Overview of the Alliance for Cellular Signaling.

Journal Article Nature · December 12, 2002 The Alliance for Cellular Signaling is a large-scale collaboration designed to answer global questions about signalling networks. Pathways will be studied intensively in two cells--B lymphocytes (the cells of the immune system) and cardiac myocytes--to fac ... Full text Link to item Cite

Activation of Gz attenuates Rap1-mediated differentiation of PC12 cells.

Journal Article J Biol Chem · November 8, 2002 Featured Publication We previously identified a specific activation-dependent interaction between the alpha subunit of the heterotrimeric G protein, G(z), and a regulator of Rap1 signaling, Rap1GAP (Meng, J., Glick, J. L., Polakis, P., and Casey, P. J. (1999) J. Biol. Chem. 27 ... Full text Link to item Cite

Stereospecificity and kinetic mechanism of human prenylcysteine lyase, an unusual thioether oxidase.

Journal Article J Biol Chem · October 25, 2002 Featured Publication Prenylated proteins contain either a 15-carbon farnesyl or a 20-carbon geranylgeranyl isoprenoid covalently attached to cysteine residues at or near their C terminus. The cellular abundance of prenylated proteins, as well as the stability of the thioether ... Full text Link to item Cite

Prenylcysteine lyase deficiency in mice results in the accumulation of farnesylcysteine and geranylgeranylcysteine in brain and liver.

Journal Article J Biol Chem · October 11, 2002 In in vitro experiments, prenylcysteine lyase (Pcly) cleaves the thioether bond of prenylcysteines to yield free cysteine and the aldehyde of the isoprenoid lipid. However, the importance of this enzyme has not yet been fully defined at the biochemical or ... Full text Link to item Cite

Reaction path of protein farnesyltransferase at atomic resolution.

Journal Article Nature · October 10, 2002 Featured Publication Protein farnesyltransferase (FTase) catalyses the attachment of a farnesyl lipid group to numerous essential signal transduction proteins, including members of the Ras superfamily. The farnesylation of Ras oncoproteins, which are associated with 30% of hum ... Full text Link to item Cite

Galpha12 and Galpha13 negatively regulate the adhesive functions of cadherin.

Journal Article J Biol Chem · July 5, 2002 Featured Publication Cadherins function to promote adhesion between adjacent cells and play critical roles in such cellular processes as development, tissue maintenance, and tumor suppression. We previously demonstrated that heterotrimeric G proteins of the G12 subfamily compr ... Full text Link to item Cite

The interaction of RGSZ1 with SCG10 attenuates the ability of SCG10 to promote microtubule disassembly.

Journal Article J Biol Chem · May 17, 2002 Featured Publication RGS proteins (regulators of G protein signaling) are a diverse family of proteins that act to negatively regulate signaling by heterotrimeric G proteins. Initially characterized as GTPase-activating proteins for Galpha subunits, recent data have implied ad ... Full text Link to item Cite

Absence of the CAAX endoprotease Rce1: effects on cell growth and transformation.

Journal Article Mol Cell Biol · January 2002 Featured Publication After isoprenylation, the Ras proteins and other CAAX proteins undergo two additional enzymatic modifications-endoproteolytic release of the last three amino acids of the protein by the protease Rce1 and methylation of the carboxyl-terminal isoprenylcystei ... Full text Link to item Cite

Prenylation of CaaX-type proteins: Basic principles through clinical applications

Journal Article Current Topics in Membranes · January 1, 2002 Post-translational modification by attachment of lipid moieties is critical for the biological activity of many membrane-associated proteins. This process, termed lipidation, serves to direct and anchor specific proteins to the cell membrane and can also p ... Full text Cite

Lysine(164)alpha of protein farnesyltransferase is important for both CaaX substrate binding and catalysis.

Journal Article Biochem J · December 15, 2001 Protein farnesyltransferase (FTase) catalyses the formation of a thioether linkage between proteins containing a C-terminal CaaX motif and a 15-carbon isoprenoid. The involvement of substrates such as oncogenic Ras proteins in tumour formation has led to i ... Full text Link to item Cite

1 Mechanism of catalysis by protein farnesyltransferase

Journal Article Enzymes · December 1, 2001 Full text Cite

Distinct regions of the cadherin cytoplasmic domain are essential for functional interaction with Galpha 12 and beta-catenin.

Journal Article J Biol Chem · November 23, 2001 Featured Publication Heterotrimeric G proteins of the G(12) subfamily mediate cellular signals leading to events such as cytoskeletal rearrangements, cell proliferation, and oncogenic transformation. Several recent studies have revealed direct effector proteins through which G ... Full text Link to item Cite

Phosphorylation and nuclear translocation of a regulator of G protein signaling (RGS10).

Journal Article J Biol Chem · August 31, 2001 Featured Publication Heterotrimeric G proteins are involved in the transduction of hormonal and sensory signals across plasma membranes of eukaryotic cells. Hence, they are a critical point of control for a variety of agents that modulate cellular function. Activation of these ... Full text Link to item Cite

Isoprenylcysteine carboxyl methyltransferase deficiency in mice.

Journal Article J Biol Chem · February 23, 2001 Featured Publication After isoprenylation, Ras and other CAAX proteins undergo endoproteolytic processing by Rce1 and methylation of the isoprenylcysteine by Icmt (isoprenylcysteine carboxyl methyltransferase). We reported previously that Rce1-deficient mice died during late g ... Full text Link to item Cite

Non-peptidic, non-prenylic inhibitors of the prenyl protein-specific protease Rce1.

Journal Article Bioorg Med Chem Lett · February 12, 2001 Several compounds designed as bisubstrate analogues of protein farnesyltransferase inhibited the prenyl protein-specific protease Rce1, qualifying them as lead structures for a novel class of non-peptidic, non-prenylic inhibitors of this protease. ... Full text Link to item Cite

Farnesylation of nonpeptidic thiol compounds by protein farnesyltransferase.

Journal Article Biochemistry · January 30, 2001 Protein farnesyltransferase catalyzes the modification of protein substrates containing specific carboxyl-terminal Ca(1)a(2)X motifs with a 15-carbon farnesyl group. The thioether linkage is formed between the cysteine of the Ca(1)a(2)X motif and C1 of the ... Full text Link to item Cite

Lysosomal prenylcysteine lyase is a FAD-dependent thioether oxidase.

Journal Article J Biol Chem · January 26, 2001 Prenylated proteins contain either a 15-carbon farnesyl or a 20-carbon geranylgeranyl isoprenoid covalently attached via a thioether bond to a cysteine residue at or near their C terminus. As prenylated proteins comprise up to 2% of the total protein in eu ... Full text Link to item Cite

Interaction of Galpha 12 and Galpha 13 with the cytoplasmic domain of cadherin provides a mechanism for beta -catenin release.

Journal Article Proc Natl Acad Sci U S A · January 16, 2001 Featured Publication The G12 subfamily of heterotrimeric G proteins, comprised of the alpha-subunits Galpha12 and Galpha13, has been implicated as a signaling component in cellular processes ranging from cytoskeletal changes to cell growth and oncogenesis. In an attempt to elu ... Full text Link to item Cite

The C-terminal polylysine region and methylation of K-Ras are critical for the interaction between K-Ras and microtubules.

Journal Article J Biol Chem · December 29, 2000 After synthesis in the cytosol, Ras proteins must be targeted to the inner leaflet of the plasma membrane for biological activity. This targeting requires a series of C-terminal posttranslational modifications initiated by the addition of an isoprenoid lip ... Full text Link to item Cite

Conversion of Tyr361 beta to Leu in mammalian protein farnesyltransferase impairs product release but not substrate recognition.

Journal Article Biochemistry · November 14, 2000 Protein farnesyltransferase catalyzes the lipid modification of protein substrates containing Met, Ser, Gln, or Ala at their C-terminus. A closely related enzyme, protein geranylgeranyltransferase type I, carries out a similar modification of protein subst ... Full text Link to item Cite

Targeted inactivation of the isoprenylcysteine carboxyl methyltransferase gene causes mislocalization of K-Ras in mammalian cells.

Journal Article J Biol Chem · June 9, 2000 After isoprenylation and endoproteolytic processing, the Ras proteins are methylated at the carboxyl-terminal isoprenylcysteine. The importance of isoprenylation for targeting of Ras proteins to the plasma membrane is well established, but the importance o ... Full text Link to item Cite

The basis for K-Ras4B binding specificity to protein farnesyltransferase revealed by 2 A resolution ternary complex structures.

Journal Article Structure · February 15, 2000 BACKGROUND: The protein farnesyltransferase (FTase) catalyzes addition of the hydrophobic farnesyl isoprenoid to a cysteine residue fourth from the C terminus of several protein acceptors that are essential for cellular signal transduction such as Ras and ... Full text Link to item Cite

Functional interaction between Galpha(z) and Rap1GAP suggests a novel form of cellular cross-talk.

Journal Article J Biol Chem · December 17, 1999 G(z) is a member of the G(i) family of trimeric G proteins whose primary role in cell physiology is still unknown. In an ongoing effort to elucidate the cellular functions of G(z), the yeast two-hybrid system was employed to identify proteins that specific ... Full text Link to item Cite

Cloning, expression, and cellular localization of a human prenylcysteine lyase.

Journal Article J Biol Chem · December 10, 1999 Prenylated proteins contain either a 15-carbon farnesyl or 20-carbon geranylgeranyl isoprenoid covalently attached to cysteine residues at or near their C terminus. These proteins constitute up to 2% of total cellular protein in eukaryotic cells. The degra ... Full text Link to item Cite

Cloning and characterization of a mammalian prenyl protein-specific protease.

Journal Article J Biol Chem · March 26, 1999 Proteins containing C-terminal "CAAX" sequence motifs undergo three sequential post-translational processing steps: modification of the cysteine with either a 15-carbon farnesyl or 20-carbon geranylgeranyl isoprenyl lipid, proteolysis of the C-terminal -AA ... Full text Link to item Cite

Disruption of the mouse Rce1 gene results in defective Ras processing and mislocalization of Ras within cells.

Journal Article J Biol Chem · March 26, 1999 Little is known about the enzyme(s) required for the endoproteolytic processing of mammalian Ras proteins. We identified a mouse gene (designated Rce1) that shares sequence homology with a yeast gene (RCE1) implicated in the proteolytic processing of Ras2p ... Full text Link to item Cite

Enzymology and biology of CaaX protein prenylation.

Journal Article Recent Prog Horm Res · 1999 Protein prenylation refers to a type of lipid modification in which either a 15-carbon farnesyl or 20-carbon geranylgeranyl isoprenoid is linked via a thioether bond to specific cysteine residues of proteins. The majority of prenylated proteins belong to a ... Link to item Cite

H-Ras peptide and protein substrates bind protein farnesyltransferase as an ionized thiolate.

Journal Article Biochemistry · November 3, 1998 The zinc metalloenzyme protein farnesyltransferase (FTase) catalyzes the alkylation of a cysteine residue of protein substrates with a 15 carbon farnesyl group. We have developed fluorescence assays to directly measure the affinity of the enzyme for peptid ... Full text Link to item Cite

RGSZ1, a Gz-selective regulator of G protein signaling whose action is sensitive to the phosphorylation state of Gzalpha.

Journal Article J Biol Chem · October 2, 1998 Regulators of G protein signaling (RGS) are a family of proteins that attenuate the activity of the trimeric G proteins. RGS proteins act as GTPase-activating proteins (GAPs) for the alpha subunits of several trimeric G proteins, much like the GAPs that re ... Full text Link to item Cite

Cocrystal structure of protein farnesyltransferase complexed with a farnesyl diphosphate substrate.

Journal Article Biochemistry · July 7, 1998 Protein farnesyltransferase (FTase) catalyzes the transfer of the hydrophobic farnesyl group from farnesyl diphosphate (FPP) to cellular proteins such as Ras at a cysteine residue near their carboxy-terminus. This process is necessary for the subcellular l ... Full text Link to item Cite

Kinetic analysis of zinc ligand mutants of mammalian protein farnesyltransferase.

Journal Article Biochemistry · March 31, 1998 Protein farnesyltransferase (FTase) is a zinc metalloenzyme that catalyzes the prenylation of several proteins that are important in cellular regulatory events. A specific residue of FTase, Cys299 in the beta subunit previously identified as essential for ... Full text Link to item Cite

Analysis of the C-terminal proteolysis of prenylated proteins

Journal Article FASEB Journal · December 1, 1997 A variety of proteins, including many GTP-binding proteins, are modified by an isoprenoid lipid which is attached at a C-terminal motif. This motif consists of the tetrapeptide CaaX, where 6C5 is the cysteine on which prenylation occurs, 6a6 are commonly a ... Cite

Substrate binding is required for release of product from mammalian protein farnesyltransferase

Journal Article FASEB Journal · December 1, 1997 Protein farnesyltransferase (FTase) catalyzes the modification by a farnesyl lipid of Ras and several other key proteins involved in cellular regulation. Previous studies on this important enzyme have indicated that product dissociation is the rate-limitin ... Cite

Structure-function analysis of residues important in zinc binding and activity in protein farnes yltransferase

Journal Article FASEB Journal · December 1, 1997 Protein farnesyltransferase (FTase) is a zinc metalloenzyme that performs a post-translational modification on many proteins that is critical for their function. The importance of cysteine residues in FTase activity was investigated using thiol-specific re ... Cite

Functions of metals in protein farnesyltransferase

Journal Article FASEB Journal · December 1, 1997 Mammalian protein farnesyltransferase (FTase) is a zinc metalloenzyme that catalyzes the addition of a farnesyl isoprenoid to a conserved cysteine in peptide or protein substrates. In addition to zinc, FTase also requires mM concentrations of magnesium for ... Cite

Prenylation-dependent association of Ki-Ras with microtubules. Evidence for a role in subcellular trafficking.

Journal Article J Biol Chem · November 28, 1997 We recently identified a prenyl peptide-binding protein in microsomal membranes from bovine brain (Thissen, J. A., and Casey, P. J. (1993) J. Biol. Chem. 268, 13780-13783). Through a variety of approaches, this binding protein has been identified as the cy ... Full text Link to item Cite

Can prenylcysteines be exploited as ligands for mammalian multidrug-resistance transporters?

Journal Article Chem Biol · October 1997 The overexpression of specific transport proteins in the membrane of many cancer cells renders these cells resistant to many therapeutic drugs. Some lipid-modified cysteine compounds inhibit one drug-transporting protein, indicating the potential of develo ... Full text Link to item Cite

Isolation and characterization of a prenylcysteine lyase from bovine brain.

Journal Article J Biol Chem · September 12, 1997 Prenylated proteins contain one of two isoprenoid lipids, either the 15-carbon farnesyl or the 20-carbon geranylgeranyl, covalently attached to cysteine residues at or near their C terminus. The cellular abundance of prenylated proteins, which can comprise ... Full text Link to item Cite

Farnesyltransferase inhibitors alter the prenylation and growth-stimulating function of RhoB.

Journal Article J Biol Chem · June 20, 1997 Protein farnesyltransferase inhibitors (FTIs) inhibit Ras transformation and Ras-dependent tumor cell growth, but the biological mechanisms underlying these activities is unclear. In previous work, we presented support for the hypothesis that the anti-tran ... Full text Link to item Cite

Substrate binding is required for release of product from mammalian protein farnesyltransferase.

Journal Article J Biol Chem · April 11, 1997 Protein farnesyltransferase (FTase) catalyzes the modification by a farnesyl lipid of Ras and several other key proteins involved in cellular regulation. Previous studies on this important enzyme have indicated that product dissociation is the rate-limitin ... Full text Link to item Cite

Crystal structure of protein farnesyltransferase at 2.25 angstrom resolution.

Journal Article Science · March 21, 1997 Protein farnesyltransferase (FTase) catalyzes the carboxyl-terminal lipidation of Ras and several other cellular signal transduction proteins. The essential nature of this modification for proper function of these proteins has led to the emergence of FTase ... Full text Link to item Cite

Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins.

Journal Article Biochem J · February 1, 1997 Pertussis toxin (PTX) has been widely used as a reagent to characterize the involvement of heterotrimeric G-proteins in signalling. This toxin catalyses the ADP-ribosylation of specific G-protein alpha subunits of the Gi family, and this modification preve ... Full text Link to item Cite

Evidence for a catalytic role of zinc in protein farnesyltransferase. Spectroscopy of Co2+-farnesyltransferase indicates metal coordination of the substrate thiolate.

Journal Article J Biol Chem · January 3, 1997 Protein farnesyltransferase (FTase) is a zinc metalloenzyme that catalyzes the addition of a farnesyl isoprenoid to a conserved cysteine in peptide or protein substrates. We have substituted the essential Zn2+ in FTase with Co2+ to investigate the function ... Full text Link to item Cite

Functions of metals in protein farnesyltransferase

Journal Article FASEB Journal · 1997 Mammalian protein farnesyltransferase (FTase) is a zinc metalloenzyme that catalyzes the addition of a farnesyl isoprenoid to a conserved cysteine in peptide or protein substrates. In addition to zinc, FTase also requires mM concentrations of magnesium for ... Cite

Substrate binding is required for release of product from mammalian protein farnesyltransferase

Journal Article FASEB Journal · 1997 Protein farnesyltransferase (FTase) catalyzes the modification by a farnesyl lipid of Ras and several other key proteins involved in cellular regulation. Previous studies on this important enzyme have indicated that product dissociation is the rate-limitin ... Cite

Analysis of the C-terminal proteolysis of prenylated proteins

Journal Article FASEB Journal · 1997 A variety of proteins, including many GTP-binding proteins, are modified by an isoprenoid lipid which is attached at a C-terminal motif. This motif consists of the tetrapeptide CaaX, where 6C5 is the cysteine on which prenylation occurs, 6a6 are commonly a ... Cite

Influence of metal ions on substrate binding and catalytic activity of mammalian protein geranylgeranyltransferase type-I.

Journal Article Biochem J · December 15, 1996 Protein geranylgeranyltransferase type-I (GGTase-I) transfers a geranylgeranyl group from the prenyl donor geranylgeranyl diphosphate (GGPP) to the cysteine residue of substrate proteins containing a C-terminal CaaX-motif (a sequence motif of proteins cons ... Full text Link to item Cite

Kinetics of protein farnesyltransferase: sigmoidal vs hyperbolic behavior as a function of assay conditions.

Journal Article Anal Biochem · December 1, 1996 Protein farnesyl transferase (FTase) catalyzes the addition of a farnesyl isoprenoid to a conserved cysteine residue in Ras and several other key proteins involved in cell regulation. An assay technique commonly used to measure FTase activity involves vacu ... Full text Link to item Cite

Prenylation of the hepatitis delta virus large antigen: a new target for farnesyltransferase inhibitors

Journal Article FASEB Journal · December 1, 1996 The hepatitis delta virus large antigen (IHDAg) is a virally encoded protein that contains a prenylation signal sequence at its carboxyl terminus consisting of the tetrapeptide Cys-Arg-Pro-Gln. The prenylation of IHDAg was examined in vitro using a fusion ... Cite

[8] Assays for G protein βγ subunit activity

Journal Article Methods in Neurosciences · December 1, 1996 Full text Cite

Identification of a cysteine residue essential for activity of protein farnesyltransferase. Cys299 is exposed only upon removal of zinc from the enzyme.

Journal Article J Biol Chem · November 8, 1996 Protein farnesyltransferase (FTase) is a zinc metalloenzyme that performs a post-translational modification on many proteins that is critical for their function. The importance of cysteine residues in FTase activity was investigated using cysteine-specific ... Full text Link to item Cite

RGS10 is a selective activator of G alpha i GTPase activity.

Journal Article Nature · September 12, 1996 Polypeptides that define a protein family termed RGS (for regulators of G-protein signalling) are encoded by the SST2 gene of the yeast Saccharomyces cerevisiae, the EGL-10 gene of the nematode Caenorhabdatis elegans, and several related mammalian genes. G ... Full text Link to item Cite

The role of prenylation in G-protein assembly and function.

Journal Article Cell Signal · September 1996 Heterotrimeric guanine nucleotide-binding regulatory proteins (G-proteins) are vital components of numerous signal transduction pathways, including sensory and hormonal response systems. G-proteins transduce signals from heptahelical transmembrane receptor ... Full text Link to item Cite

Substitution of cadmium for zinc in farnesyl:protein transferase alters its substrate specificity.

Journal Article Biochemistry · June 25, 1996 Ras proteins are mutationally activated in a variety of human cancers. Since farnesylation of Ras proteins is required for expression of their oncogenic potential, the enzyme responsible for this reaction, farnesyl:protein transferase (FPT), has become a m ... Full text Link to item Cite

Protein prenyltransferases.

Journal Article J Biol Chem · March 8, 1996 Full text Link to item Cite

The hepatitis delta virus large antigen is farnesylated both in vitro and in animal cells.

Journal Article J Biol Chem · March 1, 1996 The hepatitis delta virus large antigen (lHDAg) is a virally encoded protein that contains a prenylation signal sequence at its carboxyl terminus consisting of the tetrapeptide Cys-Arg-Pro-Gln. Although the presence of the Gln as the COOH-terminal residue ... Full text Link to item Cite

Arachidonate and related unsaturated fatty acids selectively inactivate the guanine nucleotide-binding regulatory protein, Gz.

Journal Article J Biol Chem · February 9, 1996 Gz is a member of the family of trimeric guanine nucleotide-binding regulatory proteins (G proteins), which plays a crucial role in signaling across cell membranes. The expression of Gz is predominately confined to neuronal cells and platelets, suggesting ... Full text Link to item Cite

Protein prenylation: molecular mechanisms and functional consequences.

Journal Article Annu Rev Biochem · 1996 Prenylation is a class of lipid modification involving covalent addition of either farnesyl (15-carbon) or geranylgeranyl (20-carbon) isoprenoids to conserved cysteine residues at or near the C-terminus of proteins. Known prenylated proteins include fungal ... Full text Link to item Cite

Prenylation of the hepatitis delta virus large antigen: a new target for farnesyltransferase inhibitors

Journal Article FASEB Journal · 1996 The hepatitis delta virus large antigen (IHDAg) is a virally encoded protein that contains a prenylation signal sequence at its carboxyl terminus consisting of the tetrapeptide Cys-Arg-Pro-Gln. The prenylation of IHDAg was examined in vitro using a fusion ... Cite

Evidence that direct binding of G beta gamma to the GIRK1 G protein-gated inwardly rectifying K+ channel is important for channel activation.

Journal Article Neuron · November 1995 Activation of G protein-gated K+ channels by G protein-coupled receptors contributes to parasympathetic regulation of heart rate in the atrium and inhibitory postsynaptic potentials in the peripheral and central nervous system. Having found that G beta gam ... Full text Link to item Cite

Characterization of prenylcysteines that interact with P-glycoprotein and inhibit drug transport in tumor cells.

Journal Article J Biol Chem · September 29, 1995 Prenylcysteine methyl esters that represent the C-terminal structures of prenylated proteins demonstrate specific substrate-like interactions with P-glycoprotein (Zhang, L., Sachs, C. W., Fine, R. L., and Casey, P. J. (1994) J. Biol. Chem. 269, 15973-15976 ... Full text Link to item Cite

Phosphorylation of Gz alpha by protein kinase C blocks interaction with the beta gamma complex.

Journal Article J Biol Chem · September 29, 1995 Gz alpha is a G protein alpha subunit with biochemical properties that distinguish it from other members of the G protein alpha subunit family. One such property is its ability to be stoichiometrically phosphorylated by protein kinase C (PKC), both in vitr ... Full text Link to item Cite

Protein farnesyltransferase: kinetics of farnesyl pyrophosphate binding and product release.

Journal Article Biochemistry · May 23, 1995 Protein farnesyltransferase (FTase) catalyzes the prenylation of Ras and several other key proteins involved in cell regulation. The mechanism of the FTase reaction was elucidated by pre-steady-state and steady-state kinetic analysis. FTase catalyzed the f ... Full text Link to item Cite

Protein lipidation in cell signaling.

Journal Article Science · April 14, 1995 The ability of cells to communicate with and respond to their external environment is critical for their continued existence. A universal feature of this communication is that the external signal must in some way penetrate the lipid bilayer surrounding the ... Full text Link to item Cite

Mechanisms of protein prenylation and role in G protein function.

Journal Article Biochem Soc Trans · February 1995 Full text Link to item Cite

Isolation of protein prenyltransferases from bovine brain and baculovirus expression system.

Journal Article Methods Enzymol · 1995 Full text Link to item Cite

Prenylated peptides in identification of specific binding proteins.

Journal Article Methods Enzymol · 1995 Full text Link to item Cite

Lipid modifications of protein: Preface

Journal Article Methods in Enzymology · January 1, 1995 Full text Cite

Properties and kinetic mechanism of recombinant mammalian protein geranylgeranyltransferase type I.

Journal Article J Biol Chem · September 23, 1994 Protein geranylgeranyltransferase type I (GGTase I) catalyzes the prenylation of a number of proteins that play important roles in cellular signaling. The recent cDNA cloning of this enzyme (Zhang, F. L., Diehl, R. E., Kohl, N. E., Gibbs, J. B., Giros, B., ... Link to item Cite

A G-protein beta gamma-subunit-responsive phosphoinositide 3-kinase activity in human platelet cytosol.

Journal Article J Biol Chem · June 17, 1994 Thrombin activates phosphoinositide 3-kinase (PI 3-kinase) in platelets via a mechanism involving G-proteins, possibly of both the heterotrimeric and the low molecular weight families. We have investigated the regulation of PI 3-kinase present in platelet ... Link to item Cite

Interaction of prenylcysteine methyl esters with the multidrug resistance transporter.

Journal Article J Biol Chem · June 10, 1994 The multidrug resistance transporter is an integral membrane protein, termed P-glycoprotein, which can function as an ATP-dependent drug efflux pump to reduce intracellular drug accumulation in treated cells. The physiologic function of this protein in nor ... Link to item Cite

Subtype-specific binding of azidoanilido-GTP by purified G protein alpha subunits.

Journal Article Biochemistry · June 7, 1994 Azidoanilido-GTP (AA-GTP), a hydrolysis-resistant, photoreactive GTP analog, is becoming an increasingly popular tool for identifying activation of specific G proteins by receptors within native plasma membranes. Despite the use of AA-GTP as an affinity pr ... Full text Link to item Cite

Lipid modifications of G proteins.

Journal Article Curr Opin Cell Biol · April 1994 Covalent attachment of lipids is a near-universal mechanism through which eukaryotic cells direct and, in some cases, control membrane localization of G proteins. Studies conducted over the past year have substantially advanced our understanding of both th ... Full text Link to item Cite

In vitro processing of recombinant G protein gamma subunits. Requirements for assembly of an active beta gamma complex.

Journal Article J Biol Chem · March 25, 1994 The gamma subunits of the heterotrimeric G proteins (G gamma) are subject to carboxyl-terminal processing. This processing involves prenylation of a cysteine residue initially 4 amino acids from the carboxyl terminus, endoproteolytic truncation of the 3 te ... Link to item Cite

cDNA cloning and expression of rat and human protein geranylgeranyltransferase type-I.

Journal Article J Biol Chem · February 4, 1994 Protein geranylgeranyltransferase type-I (GGTase-I) transfers a geranylgeranyl group to the cysteine residue of candidate proteins containing a carboxyl-terminal CAAX (C, cysteine; A, aliphatic amino acid; X, any amino acid) motif in which the "X" residue ... Link to item Cite

Prenylation and G protein signaling.

Journal Article Recent Prog Horm Res · 1994 Full text Link to item Cite

Microsomal membranes contain a high affinity binding site for prenylated peptides.

Journal Article J Biol Chem · July 5, 1993 Prenylation and subsequent processing of many proteins involved in cellular signaling serves to direct and/or anchor these proteins to specific membranes in the cell. One major class of prenylated proteins contains the so-called CAAX motif; such proteins c ... Link to item Cite

High level expression of mammalian protein farnesyltransferase in a baculovirus system. The purified protein contains zinc.

Journal Article J Biol Chem · May 5, 1993 The mammalian enzyme protein farnesyltransferase is a heterodimeric protein that catalyzes the addition of a farnesyl isoprenoid to a cysteine in ras proteins. Since oncogenic forms of ras proteins require the farnesyl group for transforming activity, the ... Link to item Cite

Biochemistry of protein prenylation.

Journal Article J Lipid Res · December 1992 Link to item Cite

G proteins. Visual differences.

Journal Article Nature · October 22, 1992 Full text Link to item Cite

Farnesylation of YDJ1p is required for function at elevated growth temperatures in Saccharomyces cerevisiae.

Journal Article J Biol Chem · September 15, 1992 The Saccharomyces cerevisiae YDJ1 protein (YDJ1p) contains a C-terminal "CaaX box" motif common to proteins that are modified by prenylation. In the present study we show that YDJ1p is a specific substrate for both yeast and mammalian protein farnesyltrans ... Link to item Cite

Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors.

Journal Article Science · August 28, 1992 The rate and extent of the agonist-dependent phosphorylation of beta 2-adrenergic receptors and rhodopsin by beta-adrenergic receptor kinase (beta ARK) are markedly enhanced on addition of G protein beta gamma subunits. With a model peptide substrate it wa ... Full text Link to item Cite

Mammalian protein geranylgeranyltransferase. Subunit composition and metal requirements.

Journal Article J Biol Chem · August 25, 1992 An enzyme capable of specifically modifying, with a geranylgeranyl isoprenoid, candidate proteins containing a consensus prenylation sequence ending in leucine has been purified from bovine brain. This protein geranylgeranyltransferase (PGGT), isolated usi ... Link to item Cite

Rac1, a low-molecular-mass GTP-binding-protein with high intrinsic GTPase activity and distinct biochemical properties.

Journal Article Eur J Biochem · June 1, 1992 Rac1, a member of the family of low-molecular-mass GTP-binding proteins, functions in phagocytic leukocytes as a component necessary for activation of the respiratory burst. To characterize the biochemical properties of rac1, the protein was expressed as a ... Full text Link to item Cite

Evidence of a role for heterotrimeric GTP-binding proteins in endosome fusion.

Journal Article Science · March 27, 1992 Guanosine triphosphate (GTP)-binding proteins are required for intracellular vesicular transport. Mastoparan is a peptide component of wasp venom that increases nucleotide exchange in some classes of G alpha subunits of regulatory heterotrimeric GTP-bindin ... Full text Link to item Cite

Phosphorylation of Gz in human platelets. Selectivity and site of modification.

Journal Article J Biol Chem · November 15, 1991 We have demonstrated previously that the G protein alpha subunit Gz alpha (or Gx alpha) in human platelets is subject to phosphorylation by agents that activate protein kinase C, including phorbol 12-myristate 13-acetate, thrombin, and the thromboxane A2 a ... Link to item Cite

Enzymatic modification of proteins with a geranylgeranyl isoprenoid.

Journal Article Proc Natl Acad Sci U S A · October 1, 1991 The prenylation of several proteins involved in oncogenesis and signal transduction plays an essential role in regulating their biological activities. Two distinct isoprenoids are known to be involved in this modification, the 15-carbon farnesyl and 20-car ... Full text Link to item Cite

Protein farnesyltransferase and geranylgeranyltransferase share a common alpha subunit.

Journal Article Cell · May 3, 1991 Mammalian farnesyltransferase, which attaches a 15 carbon isoprenoid, farnesyl, to a cysteine in p21ras proteins, contains two subunits, alpha and beta. The beta subunit is known to bind p21ras proteins. We show here that the alpha subunit is shared with a ... Full text Link to item Cite

The COOH-terminal domain of the Rap1A (Krev-1) protein is isoprenylated and supports transformation by an H-Ras:Rap1A chimeric protein.

Journal Article Mol Cell Biol · March 1991 Although the Rap1A protein resembles the oncogenic Ras proteins both structurally and biochemically, Rap1A exhibits no oncogenic properties. Rather, overexpression of Rap1A can reverse Ras-induced transformation of NIH 3T3 cells. Because the greatest diver ... Full text Link to item Cite

Assay of G-protein beta gamma-subunit complex by catalytic support of ADP-ribosylation of Go alpha.

Journal Article Methods Enzymol · 1991 Full text Link to item Cite

Novel localization of a G protein, Gz-alpha, in neurons of brain and retina.

Journal Article J Neurosci · August 1990 Recently, a cDNA coding for a novel G protein alpha-subunit, Gz-alpha, was isolated from a human retinal cDNA library and shown by Northern blot analysis to be expressed at high levels in neural tissues. We have prepared affinity-purified antibodies specif ... Full text Link to item Cite

G protein gamma subunits contain a 20-carbon isoprenoid.

Journal Article Proc Natl Acad Sci U S A · August 1990 A small subset of cellular proteins are covalently modified by the addition of isoprenoid groups. These include p21ras, fungal mating factors, and nuclear lamins, which are isoprenylated at carboxyl-terminal cysteine residues with a 15-carbon farnesyl grou ... Full text Link to item Cite

Inhibition of purified p21ras farnesyl:protein transferase by Cys-AAX tetrapeptides.

Journal Article Cell · July 13, 1990 We report the identification, purification, and characterization of a farnesyl:protein transferase that transfers the farnesyl moiety from farnesyl pyrophosphate to a cysteine in p21ras proteins. The enzyme was purified approximately 60,000-fold from rat b ... Full text Link to item Cite

Gz, a guanine nucleotide-binding protein with unique biochemical properties.

Journal Article J Biol Chem · February 5, 1990 Cloning of a complementary DNA (cDNA) for Gz alpha, a newly appreciated member of the family of guanine nucleotide-binding regulatory proteins (G proteins), has allowed preparation of specific antisera to identify the protein in tissues and to assay it dur ... Link to item Cite

Structural characterization of prenyl groups attached to proteins

Journal Article Methods · January 1, 1990 Certain mammalian proteins are modified at a carboxyl-terminal cysteine by a thioether-linked prenyl group, the 15-carbon farnesyl or the 20-carbon geranylgeranyl moiety. Here, we describe analytical methods to determine the presence of a prenyl modificati ... Full text Cite

p21ras is modified by a farnesyl isoprenoid.

Journal Article Proc Natl Acad Sci U S A · November 1989 Association of oncogenic ras proteins with cellular membranes appears to be a crucial step in transformation, ras is synthesized as a cytosolic precursor, which is processed to a mature form that localizes to the plasma membrane. This processing involves, ... Full text Link to item Cite

G proteins control diverse pathways of transmembrane signaling.

Journal Article FASEB J · August 1989 Hormones, neurotransmitters, and autacoids interact with specific receptors and thereby trigger a series of molecular events that ultimately produce their biological effects. These receptors, localized in the plasma membrane, carry binding sites for ligand ... Link to item Cite

G protein beta gamma subunits from bovine brain and retina: equivalent catalytic support of ADP-ribosylation of alpha subunits by pertussis toxin but differential interactions with Gs alpha.

Journal Article Biochemistry · January 24, 1989 We have examined the ability of the beta gamma subunits of guanine nucleotide binding regulatory proteins (G proteins) to support the pertussis toxin (PT) catalyzed ADP-ribosylation of G protein alpha subunits. Substoichiometric amounts of the beta gamma c ... Full text Link to item Cite

G protein involvement in receptor-effector coupling.

Journal Article J Biol Chem · February 25, 1988 Link to item Cite

Role of G proteins in transmembrane signaling.

Conference Cold Spring Harb Symp Quant Biol · 1988 Full text Link to item Cite

Role of G proteins in transmembrane signaling

Journal Article Cold Spring Harbor Symposia on Quantitative Biology · 1988 Cite

Myristoylated alpha subunits of guanine nucleotide-binding regulatory proteins.

Journal Article Proc Natl Acad Sci U S A · November 1987 Antisera directed against specific subunits of guanine nucleotide-binding regulatory proteins (G proteins) were used to immunoprecipitate these polypeptides from metabolically labeled cells. This technique detects, in extracts of a human astrocytoma cell l ... Full text Link to item Cite

Purification of adenylosuccinate lyase from rat skeletal muscle by a novel affinity column. Stabilization of the enzyme, and effects of anions and fluoro analogues of the substrate.

Journal Article Biochem J · September 1, 1987 Adenylosuccinate lyase from rat skeletal muscle was purified to apparent homogeneity by a combination of ion-exchange chromatography and affinity chromatography on agarose containing covalently bound adenylophosphonopropionate. The purified enzyme is stabl ... Full text Link to item Cite

Expression of cDNAs for G proteins in Escherichia coli. Two forms of Gs alpha stimulate adenylate cyclase.

Journal Article J Biol Chem · August 15, 1987 Complementary DNAs that encode two forms of the alpha subunit (Gs alpha) of the guanine nucleotide-binding protein responsible for stimulation of adenylate cyclase (Gs) have been inserted into plasmid vectors for expression in Escherichia coli. Following t ... Link to item Cite

Inhibition of adenylosuccinate lyase by L-alanosyl-5-aminoimidazole-4-carboxylic acid ribonucleotide (alanosyl-AICOR).

Journal Article Biochem Pharmacol · March 1, 1987 L-Alanosyl-5-aminoimidazole-4-carboxylic acid ribonucleotide (alanosyl-AICOR) has been synthesized enzymatically using 4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide (SAICAR) synthetase in conjunction with 5-aminoimidazole-4-carboxylic acid ri ... Full text Link to item Cite

Metabolism of threo-beta-fluoroaspartate by H4 cells. Inhibition of adenylosuccinate lyase by fluoro analogs of its substrates.

Journal Article J Biol Chem · October 15, 1986 DL-threo-beta-Fluoroaspartate is a substrate for the two enzymes in de novo purine biosynthesis that use aspartate, namely 4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide (SAICAR) synthetase and adenylosuccinate synthetase. With both enzymes, V ... Link to item Cite

Purification and characterization of adenylosuccinate lyase from rat skeletal muscle

Journal Article Federation Proceedings · January 1, 1985 Cite