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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cardiovascular and Renal Study Section (CVB)
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Ernest Gallo Clinic and Research Center
United States
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