PKCθ-Mediated PDK1 Phosphorylation Enhances T Cell Activation by Increasing PDK1 Stability.
PDK1 is essential for T cell receptor (TCR)-mediated activation of NF-κB, and PDK1-induced phosphorylation of PKCθ is important for TCR-induced NF-κB activation. However, inverse regulation of PDK1 by PKCθ during T cell activation has not been investigated. In this study, we found that PKCθ is involved in human PDK1 phosphorylation and that its kinase activity is crucial for human PDK1 phosphorylation. Mass spectrometry analysis of wild-type PKCθ or of kinase-inactive form of PKCθ revealed that PKCθ induced phosphorylation of human PDK1 at Ser-64. This PKCθ-induced PDK1 phosphorylation positively regulated T cell activation and TCR-induced NF-κB activation. Moreover, phosphorylation of human PDK1 at Ser-64 increased the stability of human PDK1 protein. These results suggest that Ser-64 is an important phosphorylation site that is part of a positive feedback loop for human PDK1-PKCθ-mediated T cell activation.
School of Life Sciences and Cell Logistics Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.
Jung-Ah
JA
Kang
School of Life Sciences and Cell Logistics Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.
Hyunwoo
H
Choi
School of Life Sciences and Cell Logistics Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.
Taewoo
T
Yang
School of Life Sciences and Cell Logistics Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.|Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.
Steve K
SK
Cho
School of Life Sciences and Cell Logistics Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.
Zee-Yong
ZY
Park
School of Life Sciences and Cell Logistics Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.|Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.
Sung-Gyoo
SG
Park
D000595:Amino Acid Sequence; D004795:Enzyme Stability; D057809:HEK293 Cells; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D007527:Isoenzymes / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000276:immunology* / Q000378:metabolism; D000074121:Protein Kinase C-theta; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D014162:Transfection
D007376:Interleukin-2; D007527:Isoenzymes; D016328:NF-kappa B; C000631429:PDK1 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012694:Serine; D017346:Protein Serine-Threonine Kinases; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta
PDK1; PKCθ; T cell; phosphorylation