Protein kinase C betaII regulates Akt phosphorylation on Ser-473 in a cell type- and stimulus-specific fashion.
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 PKCbetaII, can regulate Akt activity by directly phosphorylating Ser-473 in vitro and in IgE/antigen-stimulated mast cells. By contrast, PKCbeta 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, PKCbetaII appears to work as a cell type- and stimulus-specific PDK2.
Kawakami
Yuko
Y
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Nishimoto
Hajime
H
Kitaura
Jiro
J
Maeda-Yamamoto
Mari
M
Kato
Roberta M
RM
Littman
Dan R
DR
Leitges
Michael
M
Rawlings
David J
DJ
Kawakami
Toshiaki
T
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002478:Cells, Cultured; D004789:Enzyme Activation; D007073:Immunoglobulin E / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D064546:Protein Kinase C beta; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D017455:Receptors, IgE / Q000378:metabolism; D012694:Serine / Q000378:metabolism*
D007376:Interleukin-2; D007527:Isoenzymes; D010703:Phorbol Esters; D011518:Proto-Oncogene Proteins; D017455:Receptors, IgE; D007073:Immunoglobulin E; D012694:Serine; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D064546:Protein Kinase C beta