Kang Jung-Ah, Choi Hyunwoo, Yang Taewoo, Cho Steve K, Park Zee-Yong, Park Sung-Gyoo
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.
Mol Cells. 2017 Jan;40(1):37-44. doi: 10.14348/molcells.2017.2236. Epub 2017 Jan 26.
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.
PDK1对于T细胞受体（TCR）介导的NF-κB激活至关重要，并且PDK1诱导的PKCθ磷酸化对于TCR诱导的NF-κB激活很重要。然而，在T细胞激活过程中PKCθ对PDK1的反向调节尚未得到研究。在本研究中，我们发现PKCθ参与人PDK1的磷酸化，并且其激酶活性对于人PDK1的磷酸化至关重要。对野生型PKCθ或PKCθ的激酶失活形式进行质谱分析表明，PKCθ诱导人PDK1在Ser-64处发生磷酸化。这种PKCθ诱导的PDK1磷酸化正向调节T细胞激活和TCR诱导的NF-κB激活。此外，人PDK1在Ser-64处的磷酸化增加了人PDK1蛋白的稳定性。这些结果表明，Ser-64是一个重要的磷酸化位点，是人类PDK1-PKCθ介导的T细胞激活正反馈环的一部分。
