Research article summary (published 3 Dec 2006):

Competitive binding of protein kinase Calpha to membranes and Rho GTPases.

Full Abstract

Previously, we have shown that protein kinase C (PKC) forms a direct high-affinity, isozyme-specific and membrane lipid-independent interaction with Rho GTPases [Slater, S. J., Seiz, J. L., Stagliano, B. A., and Stubbs, C. D. (2001) Biochemistry 40, 4437-4445]. Since the cellular activation of PKCalpha involves an initial translocation from cytosolic to membrane compartments, the present study investigates the interdependence between the direct protein-protein interaction of PKCalpha with the Rho GTPase, Cdc42, and the protein-lipid interactions of PKCalpha with membranes. It was hypothesized that the interaction of PKCalpha with membrane-bound Cdc42 would contribute to the overall membrane-binding affinity of the kinase by providing an additional anchor. However, it was found that the incorporation of isoprenylated Cdc42 into membranes resulted in an apparent decrease in the membrane-binding affinity of PKCalpha, whereas the association of PKCbetaI, PKCdelta, PKCepsilon, and PKCzeta was each unaffected. The presence of membrane-bound Cdc42 resulted in a rightward shift in both the PS- and Ca2+-concentration response curves for PKCalpha membrane association and for the ensuing activation, whereas the maximal levels of binding and activation attained at saturating PS and Ca2+ concentrations were in each case unaffected. Overall, these findings suggest that PKCalpha undergoes a isozyme-specific interaction with membrane-bound Cdc42 to form a PKCalpha-Cdc42 complex, which possesses a membrane-binding affinity that is reduced relative to that of the individual components due to competition between Cdc42 and PS/Ca2+ for binding to PKCalpha. Consistent with this, it was found that the interaction of PKCalpha with membrane-bound Cdc42 was accompanied by the physical dissociation of the PKCalpha-Cdc42 complex from membranes. Thus, the study provides a novel mechanism by which the membrane association and activation of PKCalpha and Cdc42 may be regulated by competing protein-protein and protein-lipid interactions.

Author information

Author/s: Cook, Anthony C (AC); Ho, Cojen (C); Kershner, Jennifer L (JL); Malinowski, Steve A (SA); Moldveen, Heath (H); Stagliano, Brigid A (BA); Slater, Simon J (SJ);

Affiliation: Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

Grants: AA010968 (Agency:NIAAA NIH HHS) ; AA010990 (Agency:NIAAA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Biochemistry (Biochemistry), published in United States. (Language: eng)

Reference: 2006-Dec; vol 45 (issue 48) : pp 14452-65

Dates: Created 2006/11/28; Completed 2007/01/18; Revised 2007/12/03;

PMID: 17128984, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals Binding, Competitive Calcium - pharmacology Cell Line Cell Membrane - drug effects; metabolism Enzyme Activation - drug effects

Protein Binding Protein Kinase C-alpha - genetics; metabolism Spodoptera Surface Plasmon Resonance cdc42 GTP-Binding Protein - metabolism rho GTP-Binding Proteins - metabolism

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Calcium (7440-70-2) ; Protein Kinase C-alpha (EC 2.7.1.37) ; cdc42 GTP-Binding Protein (EC 3.6.5.2) ; rho GTP-Binding Proteins (EC 3.6.5.2)

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