Anthony Ross Means

Journal article Cell Metab · May 2008 Featured Publication Detailed knowledge of the pathways by which ghrelin and leptin signal to AMPK in hypothalamic neurons and lead to regulation of appetite and glucose homeostasis is central to the development of effective means to combat obesity. Here we identify CaMKK2 as ... Full text Link to item Cite

Degradation of the tumor suppressor PML by Pin1 contributes to the cancer phenotype of breast cancer MDA-MB-231 cells.

Journal article Mol Cell Biol · February 2008 Featured Publication Promyelocytic leukemia protein (PML) is an important regulator due to its role in numerous cellular processes including apoptosis, viral infection, senescence, DNA damage repair, and cell cycle regulation. Despite the role of PML in many cellular functions ... Full text Link to item Cite

Calmodulin-dependent kinase IV links Toll-like receptor 4 signaling with survival pathway of activated dendritic cells.

Journal article Blood · January 15, 2008 Featured Publication Microbial products, including lipopolysaccharide (LPS), an agonist of Toll-like receptor 4 (TLR4), regulate the lifespan of dendritic cells (DCs) by largely undefined mechanisms. Here, we identify a role for calcium-calmodulin-dependent kinase IV (CaMKIV) ... Full text Link to item Cite

Genotoxic stress regulates expression of the proto-oncogene Bcl6 in germinal center B cells.

Journal article Nat Immunol · October 2007 Featured Publication Antigen-specific B cells are selected in germinal centers, the structure in which these cells proliferate while accomplishing genome-remodeling processes such as class-switch recombination and somatic hypermutation. These events are associated with conside ... Full text Link to item Cite

PIN1, the cell cycle and cancer.

Journal article Nat Rev Cancer · May 2007 Featured Publication PIN1 is a peptidyl-prolyl isomerase that can alter the conformation of phosphoproteins and so affect protein function and/or stability. PIN1 regulates a number of proteins important for cell-cycle progression and, based on gain- and loss-of-function studie ... Full text Link to item Cite

Physiological roles of the Ca2+/CaM-dependent protein kinase cascade in health and disease.

Journal article Subcell Biochem · 2007 Featured Publication Numerous hormones, growth factors and physiological processes cause a rise in cytosolic Ca2+, which is translated into meaningful cellular responses by interacting with a large number of Ca2(+)-binding proteins. The Ca2(+)-binding protein that is most perv ... Full text Link to item Cite

Regulation of AMP-activated protein kinase by multisite phosphorylation in response to agents that elevate cellular cAMP.

Journal article J Biol Chem · December 1, 2006 Featured Publication The AMP-activated protein kinase (AMPK) and cAMP signaling systems are both key regulators of cellular metabolism. In this study, we show that AMPK activity is attenuated in response to cAMP-elevating agents through modulation of at least two of its alpha ... Full text Link to item Cite

Rho kinase differentially regulates phosphorylation of nonmuscle myosin II isoforms A and B during cell rounding and migration.

Journal article J Biol Chem · November 24, 2006 Featured Publication The actin-myosin cytoskeleton is generally accepted to produce the contractile forces necessary for cellular processes such as cell rounding and migration. All vertebrates examined to date are known to express at least two isoforms of non-muscle myosin II, ... Full text Link to item Cite

Ubiquitylation of cyclin E requires the sequential function of SCF complexes containing distinct hCdc4 isoforms.

Journal article Mol Cell · July 7, 2006 Featured Publication Cyclin E, an activator of cyclin-dependent kinase 2 (Cdk2), is targeted for proteasomal degradation by phosphorylation-dependent multiubiquitylation via the ubiquitin ligase SCF(hCdc4). SCF ubiquitin ligases are composed of a core of conserved subunits and ... Full text Link to item Cite

The loss of PIN1 deregulates cyclin E and sensitizes mouse embryo fibroblasts to genomic instability.

Journal article J Biol Chem · January 6, 2006 Featured Publication During the G0/G1-S phase transition, the timely synthesis and degradation of key regulatory proteins is required for normal cell cycle progression. Two of these proteins, c-Myc and cyclin E, are recognized by the Cdc4 E3 ligase of the Skp1/Cul1/Rbx1 (SCF) ... Full text Link to item Cite

Chutes and Ladders: the search for protein kinases that act on AMPK.

Journal article Trends Biochem Sci · January 2006 Featured Publication AMP-activated protein kinase (AMPK), a key regulator of energy homeostasis in mammalian cells, is, in turn, regulated by long-sought upstream protein kinases (AMPKKs). Following the recent identification of the tumor-suppressor kinase LKB1 as an AMPKK, a b ... Full text Link to item Cite

Peptidyl-prolyl isomerase 1 (Pin1) serves as a coactivator of steroid receptor by regulating the activity of phosphorylated steroid receptor coactivator 3 (SRC-3/AIB1).

Journal article Mol Cell Biol · November 2005 Featured Publication Steroid receptor coactivator 3 (SRC-3/AIB1) interacts with steroid receptors in a ligand-dependent manner to activate receptor-mediated transcription. A number of intracellular signaling pathways initiated by growth factors and hormones induce phosphorylat ... Full text Link to item Cite

Calmodulin-dependent protein kinase IV regulates hematopoietic stem cell maintenance.

Journal article J Biol Chem · September 30, 2005 Featured Publication The hematopoietic stem cell (HSC) gives rise to all mature, terminally differentiated cells of the blood. Here we show that calmodulin-dependent protein kinase IV (CaMKIV) is present in c-Kit+ ScaI+ Lin(-/low) hematopoietic progenitor cells (KLS cells) and ... Full text Link to item Cite

The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases.

Journal article J Biol Chem · August 12, 2005 Featured Publication The AMP-activated protein kinase (AMPK) is an important regulator of cellular metabolism in response to metabolic stress and to other regulatory signals. AMPK activity is absolutely dependent upon phosphorylation of AMPKalphaThr-172 in its activation loop ... Full text Link to item Cite

Calmodulin-dependent protein kinase IV regulates nuclear export of Cabin1 during T-cell activation.

Journal article EMBO J · June 15, 2005 Featured Publication Calcium signaling is critical for activation of T lymphocytes and has been proposed to be transduced through multiple calmodulin target proteins. Whereas the calcineurin-NFAT signaling module is critical for all mammalian T cells, the role of calmodulin-de ... Full text Link to item Cite

The autonomous activity of calcium/calmodulin-dependent protein kinase IV is required for its role in transcription.

Journal article J Biol Chem · May 27, 2005 Featured Publication Calcium/calmodulin-dependent kinase IV (CaMKIV) is a multifunctional serine/threonine kinase that is positively regulated by two main events. The first is the binding of calcium/calmodulin (Ca(2+)/CaM), which relieves intramolecular autoinhibition of the e ... Full text Link to item Cite

A role for Pin1 in mammalian germ cell development and spermatogenesis.

Journal article Front Biosci · September 1, 2004 Featured Publication The peptidyl-prolyl isomerase Pin1 is proposed to have diverse functions in many vital aspects of the cell. Despite the multitude of proteins targeted by Pin1 and the proposed regulatory role it plays in critical cellular functions, Pin1 is an essential ge ... Full text Link to item Cite

PINA is essential for growth and positively influences NIMA function in Aspergillus nidulans.

Journal article J Biol Chem · July 30, 2004 Featured Publication The phospho-Ser/Thr-directed prolyl-isomerase Pin1 was originally identified in vertebrate systems as a negative regulator of NIMA, a Ser/Thr protein kinase that regulates the G(2)/M transition in Aspergillus nidulans. Here we explore the physiological rol ... Full text Link to item Cite

Regulation and function of the calcium/calmodulin-dependent protein kinase IV/protein serine/threonine phosphatase 2A signaling complex.

Journal article J Biol Chem · July 23, 2004 Featured Publication Calcium/calmodulin-dependent protein kinase IV (CaMKIV) is a member of the broad substrate specificity class of Ca(2+)/calmodulin (CaM)-dependent protein kinases and functions as a potent stimulator of Ca(2+)-dependent gene expression. Activation of CaMKIV ... Full text Link to item Cite

Regulation of cyclin D1/Cdk4 complexes by calcium/calmodulin-dependent protein kinase I.

Journal article J Biol Chem · April 9, 2004 Featured Publication The selective inhibitor of the multifunctional calcium/calmodulin-dependent kinases (CaMK), KN-93, arrests a variety of cell types in G(1). However, the biochemical nature of this G(1) arrest point and the physiological target of KN-93 in G(1) remain contr ... Full text Link to item Cite

Calcineurin regulates cyclin D1 accumulation in growth-stimulated fibroblasts.

Journal article Mol Biol Cell · April 2004 Featured Publication Calcium (Ca(2+)) and calmodulin (CaM) are required for progression of mammalian cells from quiescence into S phase. In multiple cell types, cyclosporin A causes a G(1) cell cycle arrest, implicating the serine/threonine phosphatase calcineurin as one Ca(2+ ... Full text Link to item Cite

A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells.

Journal article Nat Cell Biol · April 2004 Featured Publication The stability of c-Myc is regulated by multiple Ras effector pathways. Phosphorylation at Ser 62 stabilizes c-Myc, whereas subsequent phosphorylation at Thr 58 is required for its degradation. Here we show that Ser 62 is dephosphorylated by protein phospha ... Full text Link to item Cite

Catalytic activity is required for calcium/calmodulin-dependent protein kinase IV to enter the nucleus.

Journal article J Biol Chem · March 19, 2004 Featured Publication Calcium/calmodulin-dependent protein kinase IV (CaMKIV) is a nuclear protein kinase that responds to acute rises in intracellular calcium by phosphorylating and activating proteins involved in transcription. Consistent with these roles, CaMKIV is found pre ... Full text Link to item Cite

Targeted expression of calmodulin increases ventricular cardiomyocyte proliferation and deoxyribonucleic acid synthesis during mouse development.

Journal article Endocrinology · March 2004 Featured Publication The cell signaling pathways that control ventricular cardiomyocyte proliferation during development are poorly understood. Here we show that increasing levels of the ubiquitous Ca(2+) receptor calmodulin (CaM) can regulate cardiomyocyte proliferation in vi ... Full text Link to item Cite

Regulation of cell cycle progression by calcium/calmodulin-dependent pathways.

Journal article Endocr Rev · December 2003 Featured Publication Many hormones, growth factors, and cytokines regulate proliferation of their target cells. Perhaps the most universal signaling cascades required for proliferative responses are those initiated by transient rises in intracellular calcium (Ca(2+)). The majo ... Full text Link to item Cite

Spermatogonial depletion in adult Pin1-deficient mice.

Journal article Biol Reprod · December 2003 Featured Publication Spermatogonia in the mouse testis arise from early postnatal gonocytes that are derived from primordial germ cells (PGCs) during embryonic development. The proliferation, self-renewal, and differentiation of spermatogonial stem cells provide the basis for ... Full text Link to item Cite

Pin1 regulates the timing of mammalian primordial germ cell proliferation.

Journal article Development · August 2003 Featured Publication Primordial germ cells (PGCs) give rise to male and female germ cells to transmit the genome from generation to generation. Defects in PGC development often result in infertility. In the mouse embryo, PGCs undergo proliferation and expansion during and afte ... Full text Link to item Cite

Proteomic analysis of calcium/calmodulin-dependent protein kinase I and IV in vitro substrates reveals distinct catalytic preferences.

Journal article J Biol Chem · March 21, 2003 Featured Publication The multifunctional calcium/calmodulin-dependent protein kinases I and IV (CaMKI and CaMKIV) are closely related by primary sequence and predicted to have similar substrate specificities based on peptide studies. We identified a fragment of p300-(1-117) th ... Full text Link to item Cite

Pressure overload selectively up-regulates Ca2+/calmodulin-dependent protein kinase II in vivo.

Journal article Mol Endocrinol · February 2003 Featured Publication Signals transduced by the multifunctional calcium/calmodulin-dependent protein kinases (CaMKs), have been suggested to regulate the development of hypertrophy. We address the role of the three multifunctional CaMKs, CaMK I, II, and IV, in this process usin ... Full text Link to item Cite

The peptidyl-prolyl isomerase Pin1.

Journal article Prog Cell Cycle Res · 2003 Featured Publication The phospho-Ser/Thr-Pro specific prolyl-isomerase Pin1 has been implicated in multiple aspects of cell cycle regulation. It has been suggested that Pin1 function is required for both normal mitotic progression and reentry into the cell cycle from quiescenc ... Link to item Cite

A new identity for MLK3 as an NIMA-related, cell cycle-regulated kinase that is localized near centrosomes and influences microtubule organization.

Journal article Mol Biol Cell · January 2003 Featured Publication Although conserved counterparts for most proteins involved in the G(2)/M transition of the cell cycle have been found in all eukaryotes, a notable exception is the essential but functionally enigmatic fungal kinase NIMA. While a number of vertebrate kinase ... Full text Link to item Cite

Mechanisms for regulation of calmodulin kinase IIalpha by Ca(2+)/calmodulin and autophosphorylation of threonine 286.

Journal article Biochemistry · November 26, 2002 Featured Publication A mechanism that relates calmodulin (CaM) binding to enzyme activation remains to be established within the context of full-length calmodulin kinase IIalpha (CaM KIIalpha). Previous studies using peptides and/or truncated enzymes have shown that L299 of Ca ... Full text Link to item Cite

A CaMK cascade activates CRE-mediated transcription in neurons of Caenorhabditis elegans.

Journal article EMBO Rep · October 2002 Featured Publication Calcium (Ca2+) signals regulate a diverse set of cellular responses, from proliferation to muscular contraction and neuro-endocrine secretion. The ubiquitous Ca2+ sensor, calmodulin (CaM), translates changes in local intracellular Ca2+ concentrations into ... Full text Link to item Cite

Pcp1p, an Spc110p-related calmodulin target at the centrosome of the fission yeast Schizosaccharomyces pombe.

Journal article Cell Growth Differ · February 2002 Featured Publication In the budding yeast Saccharomyces cerevisiae, the calmodulin-binding protein Spc110p/Nuf1p facilitates mitotic spindle formation from the fungal centrosome or spindle pole body (SPB). The human Spc110p orthologue kendrin is a centrosomal, calmodulin-bindi ... Link to item Cite

Calcium binding is required for calmodulin function in Aspergillus nidulans.

Journal article Eukaryot Cell · February 2002 Featured Publication To explore the structural basis for the essential role of calmodulin (CaM) in Aspergillus nidulans, we have compared the biochemical and in vivo properties of A. nidulans CaM (AnCaM) with those of heterologous CaMs. Neither Saccharomyces cerevisiae CaM (Sc ... Full text Link to item Cite

Defective signaling in a subpopulation of CD4(+) T cells in the absence of Ca(2+)/calmodulin-dependent protein kinase IV.

Journal article Mol Cell Biol · January 2002 Featured Publication Ca(2+)/calmodulin-dependent protein kinase IV-deficient (CaMKIV(-/-)) mice have been used to investigate the role of this enzyme in CD4(+) T cells. We identify a functional defect in a subpopulation of CD4(+) T cells, characterized by a cell surface marker ... Full text Link to item Cite

The modular nature of histone deacetylase HDAC4 confers phosphorylation-dependent intracellular trafficking.

Journal article J Biol Chem · September 14, 2001 Featured Publication In C2C12 myoblasts, endogenous histone deacetylase HDAC4 shuttles between cytoplasmic and nuclear compartments, supporting the hypothesis that its subcellular localization is dynamically regulated. However, upon differentiation, this dynamic equilibrium is ... Full text Link to item Cite

Spermatogenesis and the regulation of Ca(2+)-calmodulin-dependent protein kinase IV localization are not dependent on calspermin.

Journal article Mol Cell Biol · September 2001 Featured Publication Calspermin and Ca(2+)-calmodulin-dependent protein kinase IV (CaMKIV) are two proteins encoded by the Camk4 gene. CaMKIV is found in multiple tissues, including brain, thymus, and testis, while calspermin is restricted to the testis. In the mouse testis, b ... Full text Link to item Cite

Expression of Ca(2+)/calmodulin-dependent protein kinase IV (caMKIV) messenger RNA during murine embryogenesis.

Journal article Cell Growth Differ · July 2001 Featured Publication Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV) is a monomeric, multifunctional serine/threonine protein kinase that is expressed in subanatomic regions of the central and peripheral nervous system, T lymphocytes, and male germ cells. It is frequent ... Link to item Cite

Ca(2+)/CaM-dependent kinases: from activation to function.

Journal article Annu Rev Pharmacol Toxicol · 2001 Featured Publication Calmodulin (CaM) is an essential protein that serves as a ubiquitous intracellular receptor for Ca(2+). The Ca(2+)/CaM complex initiates a plethora of signaling cascades that culminate in alteration of cellular functions. Among the many Ca(2+)/CaM-binding ... Full text Link to item Cite