Activation of the Cooh-Terminal Src Kinase (Csk) by Camp-Dependent Protein Kinase Inhibits Signaling through the T Cell Receptor
作者： Torkel Vang , Knut Martin Torgersen , Vibeke Sundvold , Manju Saxena , Finn Olav Levy
关键词: Proto-oncogene tyrosine-protein kinase Src 、 Cell biology 、 T cell 、 Protein kinase A 、 Tyrosine-protein kinase CSK 、 Cancer research 、 Jurkat cells 、 T-cell receptor 、 Chemistry 、 Tyrosine phosphorylation 、 CD3
摘要: In T cells, cAMP-dependent protein kinase (PKA) type I colocalizes with the cell receptor–CD3 complex (TCR/CD3) and inhibits function via a previously unknown proximal target. Here we examine mechanism for this PKA-mediated immunomodulation. cAMP treatment of Jurkat normal cells reduces Lck-mediated tyrosine phosphorylation TCR/CD3 ζ chain after activation, decreases Lck activity. Phosphorylation residue Y505 in by COOH-terminal Src (Csk), which negatively regulates Lck, is essential inhibitory effect on phosphorylation. PKA phosphorylates Csk at S364 vitro vivo leading to two- fourfold increase activity that necessary cAMP-mediated inhibition TCR-induced interleukin 2 secretion. Both are targeted lipid rafts where activation occurs, raft-associated increased treated forskolin. We propose whereby through intersects signaling kinases activation.
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