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http://dx.doi.org/10.14348/molcells.2017.2236

PKCθ-Mediated PDK1 Phosphorylation Enhances T Cell Activation by Increasing PDK1 Stability  

Kang, Jung-Ah (School of Life Sciences and Cell Logistics Research Center, Gwangju Institute of Science and Technology (GIST))
Choi, Hyunwoo (School of Life Sciences and Cell Logistics Research Center, Gwangju Institute of Science and Technology (GIST))
Yang, Taewoo (School of Life Sciences and Cell Logistics Research Center, Gwangju Institute of Science and Technology (GIST))
Cho, Steve K. (School of Life Sciences and Cell Logistics Research Center, Gwangju Institute of Science and Technology (GIST))
Park, Zee-Yong (School of Life Sciences and Cell Logistics Research Center, Gwangju Institute of Science and Technology (GIST))
Park, Sung-Gyoo (School of Life Sciences and Cell Logistics Research Center, Gwangju Institute of Science and Technology (GIST))
Publication Information
Molecules and Cells / v.40, no.1, 2017 , pp. 37-44 More about this Journal
Abstract
PDK1 is essential for T cell receptor (TCR)-mediated activation of $NF-{\kappa}B$, and PDK1-induced phosphorylation of $PKC{\theta}$ is important for TCR-induced $NF-{\kappa}B$ activation. However, inverse regulation of PDK1 by $PKC{\theta}$ during T cell activation has not been investigated. In this study, we found that $PKC{\theta}$ is involved in human PDK1 phosphorylation and that its kinase activity is crucial for human PDK1 phosphorylation. Mass spectrometry analysis of wild-type $PKC{\theta}$ or of kinase-inactive form of $PKC{\theta}$ revealed that $PKC{\theta}$ induced phosphorylation of human PDK1 at Ser-64. This $PKC{\theta}$-induced PDK1 phosphorylation positively regulated T cell activation and TCR-induced $NF-{\kappa}B$ 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-$PKC{\theta}$-mediated T cell activation.
Keywords
PDK1; phosphorylation; $PKC{\theta}$; T cell;
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