Peptides Derived from the C2 Domain of Protein Kinase Cϵ (ϵPKC) Modulate ϵPKC Activity and Identify Potential Protein-Protein Interaction Surfaces

摘要: Peptides derived from protein kinase C (PKC) modulate its activity by interfering with critical protein-protein interactions within PKC and between PKC-binding proteins (Souroujon, M. C., Mochly-Rosen, D. (1998) Nat. Biotechnol. 16, 919-924). We previously demonstrated that the C2 domain of plays a role in these interactions. By focusing on ϵPKC using rational approach, we then identified one C2-derived peptide acts as an isozyme-selective activator another selective inhibitor ϵPKC. These peptides were used to identify protection cardiac brain ischemic damage, prevention complications diabetes, reducing pain, protecting transplanted hearts. The efficacy two led us search for additional PKC-modulating activities. Here report series 5-9-residue are regions span length tested their effect cells vivo ex model acute heart disease. Most acted activators PKC, few inhibitors. PKC-dependent myristoylated alanine-rich substrate phosphorylation knock-out revealed only subset over other isozymes. ϵPKC-selective also protective myocardium injury, ϵPKC-dependent function (Liu, G. S., Cohen, V., D., Downey, J. (1999) Mol. Cell. Cardiol. 31, 1937-1948), caused translocation isozymes when injected systemically into mice. Examination structure similar activities clustered discrete domain. propose represent surfaces and/or partner proteins; some unique ϵPKC, others common