Protein Kinase Cζ Exhibits Constitutive Phosphorylation and Phosphatidylinositol-3,4,5-Triphosphate-Independent Regulation Irene S
Biochem. J. (2016) 473, 509–523 doi:10.1042/BJ20151013 509 Protein kinase Cζ exhibits constitutive phosphorylation and phosphatidylinositol-3,4,5-triphosphate-independent regulation Irene S. Tobias*†, Manuel Kaulich‡, Peter K. Kim§, Nitya Simon*, Estela Jacinto§, Steven F. Dowdy‡, Charles C. King and Alexandra C. Newton*1 *Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, U.S.A. †Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, U.S.A. ‡Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, U.S.A. §Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, U.S.A. Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, U.S.A. Atypical protein kinase C (aPKC) isoenzymes are key modulators and insulin unresponsive, in marked contrast to the insulin- of insulin signalling, and their dysfunction correlates with insulin- dependent activation of Akt monitored by an Akt-specific reporter. resistant states in both mice and humans. Despite the engaged Nor does forced recruitment to phosphoinositides by fusing interest in the importance of aPKCs to type 2 diabetes, much the pleckstrin homology (PH) domain of Akt to the kinase less is known about the molecular mechanisms that govern their domain of PKCζ alter either the phosphorylation or activity cellular functions than for the conventional and novel PKC of PKCζ . Thus, insulin stimulation does not activate PKCζ isoenzymes and the functionally-related protein kinase B (Akt) through the canonical phosphatidylinositol-3,4,5-triphosphate- family of kinases.
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