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Patrick John Casey

James B. Duke Distinguished Professor of Pharmacology and Cancer Biology
Pharmacology & Cancer Biology
Duke Box 3813, Durham, NC 27710
Erwin Terrace II, Suite 303, 2812 Erwin Road, Durham, NC 27705

Featured Works


Structure of mammalian protein geranylgeranyltransferase type-I.

Journal article EMBO J · November 17, 2003 Featured Work 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

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 Work 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

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

Journal article J Biol Chem · November 8, 2002 Featured Work 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 Work 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

Reaction path of protein farnesyltransferase at atomic resolution.

Journal article Nature · October 10, 2002 Featured Work 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 Work 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 Work 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 Work 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

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 Work 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 Work 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 Work 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

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 Work 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