TCR-induced Akt serine 473 phosphorylation is regulated by protein kinase C-alpha.
Akt signaling plays a central role in T cell functions, such as proliferation, apoptosis, and regulatory T cell development. Phosphorylation at Ser(473) in the hydrophobic motif, along with Thr(308) in its activation loop, is considered necessary for Akt function. It is widely accepted that phosphoinositide-dependent kinase 1 (PDK-1) phosphorylates Akt at Thr(308), but the kinase(s) responsible for phosphorylating Akt at Ser(473) (PDK-2) remains elusive. The existence of PDK-2 is considered to be specific to cell type and stimulus. PDK-2 in T cells in response to TCR stimulation has not been clearly defined. In this study, we found that conventional PKC positively regulated TCR-induced Akt Ser(473) phosphorylation. PKC-alpha purified from T cells can phosphorylate Akt at Ser(473) in vitro upon TCR stimulation. Knockdown of PKC-alpha in T-cell-line Jurkat cells reduced TCR-induced phosphorylation of Akt as well as its downstream targets. Thus our results suggest that PKC-alpha is a candidate for PDK-2 in T cells upon TCR stimulation.
Yang
Lifen
L
Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
Qiao
Guilin
G
Ying
Haiyan
H
Zhang
Jian
J
Yin
Fei
F
D000818:Animals; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology*
D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011948:Receptors, Antigen, T-Cell; D012694:Serine; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D051571:Protein Kinase C-alpha