+ Most Popular
Cunninghamia lanceolata plantations in China
Mammalian lairs in paleo ecological studies and palynology
Studies on technological possibilities in utilization of anhydrous milk fat for production of recombined butter-like products
Should right-sided fibroelastomas be operated upon?
Large esophageal lipoma
Apoptosis in the mammalian thymus during normal histogenesis and under various in vitro and in vivo experimental conditions
Poissons characoides nouveaux ou non signales de l'Ilha do Bananal, Bresil
Desensitizing efficacy of Colgate Sensitive Maximum Strength and Fresh Mint Sensodyne dentifrices
Administration of fluid by subcutaneous infusion: revival of a forgotten method
Tundra mosquito control - an impossible dream?
Schizophrenia for primary care providers: how to contribute to the care of a vulnerable patient population
Geochemical pattern analysis; method of describing the Southeastern limestone regional aquifer system
Incidence of low birth weights in a hospital of Mexico City
Graded management intensity of grassland systems for enhancing floristic diversity
Microbiology and biochemistry of cheese and fermented milk
The ember tetra: a new pygmy characid tetra from the Rio das Mortes, Brazil, Hyphessobrycon amandae sp. n. (Pisces, Characoidei)
Risk factors of contrast-induced nephropathy in patients after coronary artery intervention
Renovation of onsite domestic wastewater in a poorly drained soil
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Systolic blood pressure in a population of infants in the first year of life: the Brompton study
Haematological studies in rats fed with metanil yellow
Studies on pasteurellosis. I. A new species of Pasteurella encountered in chronic fowl cholera
Dormancy breaking and germination of Acacia salicina Lindl. seeds
therapy of lupus nephritis. a two-year prospective study

Peptides derived from the C2 domain of protein kinase C epsilon (epsilon PKC) modulate epsilon PKC activity and identify potential protein-protein interaction surfaces

Peptides derived from the C2 domain of protein kinase C epsilon (epsilon PKC) modulate epsilon PKC activity and identify potential protein-protein interaction surfaces

Journal of Biological Chemistry 282(6): 4113-4123

ISSN/ISBN: 0021-9258

PMID: 17142835

DOI: 10.1074/jbc.m608521200

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

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 049884312

Download citation: RISBibTeXText

Related references

Peptides Derived from the C2 Domain of Protein Kinase C (PKC) Modulate PKC Activity and Identify Potential Protein-Protein Interaction Surfaces. The Journal of Biological Chemistry 282(6): 13-23, 2007

Interferon alpha induces protein kinase C-epsilon (PKC-epsilon) gene expression and a 4.7-kb PKC-epsilon-related transcript. Proceedings of the National Academy of Sciences of the United States of America 90(15): 6944-6948, 1993

Identification of conserved amino acids N-terminal of the PKC epsilon C1b domain crucial for protein kinase C epsilon-mediated induction of neurite outgrowth. Journal of Biological Chemistry 280(18): 17910-17919, 2005

Impact of protein kinase C-epsilon for myocardial hypertrophy after chronic pressure overload In-vivo study in protein kinase C-epsilon knockout mice. Journal of the American College of Cardiology 43(5 Suppl A): 456A, 2004

Cardioprotection by epsilon-protein kinase C activation from ischemia: continuous delivery and antiarrhythmic effect of an epsilon-protein kinase C-activating peptide. Circulation 111(1): 44-50, 2005

Detection of N-epsilon, N-epsilon, N-epsilon-trimethyllysine in ribosomal protein L 11 by methylation of E. coli ribosomes synthesized in the presence of ethionine. Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences. Serie D: Sciences Naturelles 278(7): 951-953, 1974

Role of protein kinase C-epsilon ( PKC epsilon ) in GSTT-induced cardioprotection. Zhongguo Yaolixue Tongbao 23(9): 1193-1197, 2007

Autoinhibition of casein kinase i epsilon (CKi epsilon) is relieved by protein phosphatases and limited proteolysis. Journal of Biological Chemistry 273(3): 1357-1364, 1998

Protein kinase C-epsilon (PKC-epsilon): its unique structure and function. Journal of Biochemistry 132(6): 847-852, 2002

Protein kinase C epsilon is localized to the Golgi Identification of PKC-epsilon subcellular localization domains and proteolytic degradation sites. FASEB Journal 9(6): A1408, 1995

Interaction of the C2 domain from protein kinase C(epsilon) with model membranes. Biochemistry 46(11): 3183-3192, 2007

Anti cd3 epsilon induced activation of a t h2 clone leads to down regulation of protein kinase c delta and epsilon message and cell death. FASEB Journal 4(7): A2040, 1990

Mechanisms related to the cardioprotective effects of protein kinase C epsilon (PKC epsilon) peptide activator or inhibitor in rat ischemia/reperfusion injury. Naunyn-Schmiedeberg's Archives of Pharmacology 378(1): 1-15, 2008

Protein tyrosine phosphatase epsilon modulates Ca2+ entry and Gardos channel activity in epsilon knockout mouse red cells. Blood 102(11): 253a, 2003

Theoretical and experimental studies on alpha/epsilon-hybrid peptides: design of a 14/12-helix from peptides with alternating (S)-C-linked carbo-epsilon-amino acid [(S)-epsilon-Caa((x))] and L-ala. Journal of Organic Chemistry 74(17): 6703-6713, 2009