Protein kinase C (C-Kinase) is a key enzyme in signal transduction. In the heart, C-Kinase affects contractility, secretion, cell hypertophy and myofibril structure. There are seven C-Kinase Isozymes, each of which is likely to be involved in a different function. Activation of C-Kinase isozymes results in their translocation to intracellular structures such as the cell membrane and cytoskeletal elements. Identifying which isozymes are activated in the heart and determining the intracellular location of each activated C-Kinase will lead to understanding the functional role of each isozyme. Using biochemical, immunological and immunohistochemical techniques I will determine: (1) the cellular structures to which individual C-Kinase isozymes translocate and whether C-Kinase isozymes vary in their sensitivity to activation by different hormones and neurotransmitters. (2) the protein receptor for activated C-Kinase (RACKs) in these structures and whether they are isozyme specific and (3) the sites on the C-Kinase molecule that are responsible for binding RACKs. C-Kinase is implicated in pathological conditions in the heart including hypertrophy and dysrhythmia. Thus, elucidating the functional divergence of the various C-Kinase isozymes will enable therapeutic intervention resulting from isozyme-specific modulation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL043380-04
Application #
3362029
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1989-07-01
Project End
1993-01-14
Budget Start
1992-07-07
Budget End
1993-01-14
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Ernest Gallo Clinic and Research Center
Department
Type
DUNS #
173995366
City
Emeryville
State
CA
Country
United States
Zip Code
94608
Mochly-Rosen, D; Kauvar, L M (1998) Modulating protein kinase C signal transduction. Adv Pharmacol 44:91-145
Mochly-Rosen, D; Gordon, A S (1998) Anchoring proteins for protein kinase C: a means for isozyme selectivity. FASEB J 12:35-42
Zhang, Z H; Johnson, J A; Chen, L et al. (1997) C2 region-derived peptides of beta-protein kinase C regulate cardiac Ca2+ channels. Circ Res 80:720-9
Yedovitzky, M; Mochly-Rosen, D; Johnson, J A et al. (1997) Translocation inhibitors define specificity of protein kinase C isoenzymes in pancreatic beta-cells. J Biol Chem 272:1417-20
Zhou, L Y; Disatnik, M; Herron, G S et al. (1996) Differential activation of protein kinase C isozymes by phorbol ester and collagen in human skin microvascular endothelial cells. J Invest Dermatol 107:248-52
Mochly-Rosen, D; Smith, B L; Chen, C H et al. (1995) Interaction of protein kinase C with RACK1, a receptor for activated C-kinase: a role in beta protein kinase C mediated signal transduction. Biochem Soc Trans 23:596-600
Ron, D; Luo, J; Mochly-Rosen, D (1995) C2 region-derived peptides inhibit translocation and function of beta protein kinase C in vivo. J Biol Chem 270:24180-7
Ron, D; Mochly-Rosen, D (1995) An autoregulatory region in protein kinase C: the pseudoanchoring site. Proc Natl Acad Sci U S A 92:492-6
Mochly-Rosen, D (1995) Localization of protein kinases by anchoring proteins: a theme in signal transduction. Science 268:247-51
Ron, D; Mochly-Rosen, D (1994) Agonists and antagonists of protein kinase C function, derived from its binding proteins. J Biol Chem 269:21395-8

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