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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))
  • Received : 2016.10.05
  • Accepted : 2016.12.12
  • Published : 2017.01.31

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

Acknowledgement

Supported by : Ministry of Health & Welfare, Gwangju Institute of Science and Technology, National Research Foundation of Korea

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