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Thesis Name: Protein Kinase C II Regulates Akt Phosphorylation on Ser-473 in a Cell Type- and Stimulus-specific Fashion
Usage: biochemistry
Keyword: Protein Kinase C II
Remarks: From the Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, the National Institute of Vegetables, and Tea Science, NARO, 2769 Kanaya, Shizuoka 428-8501, Japan, the ¶Departments of Immunology and Pediatrics, University of Washington, School of Medicine, Seattle, Washington 98195, and the ||Departments of Pathology and Microbiology, New York University, School of Medicine, Howard Hughes Medical Institute, New York, New York 10016

Akt (= protein kinase B), a subfamily of the AGC serine/threonine kinases, plays critical roles in survival, proliferation, glucose metabolism, and other cellular functions. Akt activation requires the recruitment of the enzyme to the plasma membrane by interacting with membrane-bound lipid products of phosphatidylinositol 3-kinase. Membrane-bound Akt is then phosphorylated at two sites for its full activation; Thr-308 in the activation loop of the kinase domain is phosphorylated by 3-phosphoinositide-dependent kinase-1 (PDK1) and Ser-473 in the C-terminal hydrophobic motif by a putative kinase PDK2. The identity of PDK2 has been elusive. Here we present evidence that conventional isoforms of protein kinase C (PKC), particularly PKCII, can regulate Akt activity by directly phosphorylating Ser-473 in vitro and in IgE/antigen-stimulated mast cells. By contrast, PKC is not required for Ser-473 phosphorylation in mast cells stimulated with stem cell factor or interleukin-3, in serum-stimulated fibroblasts, or in antigen receptor-stimulated T or B lymphocytes. Therefore, PKCII appears to work as a cell type- and stimulus-specific PDK2.

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