1. Resting lymphocyte kinase (Rlk/Txk) targets lymphoid adaptor SLP-76 in the cooperative activation of interleukin-2 transcription in T-cells.
- Author
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Schneider H, Guerette B, Guntermann C, and Rudd CE
- Subjects
- Adaptor Proteins, Signal Transducing, Animals, COS Cells, Humans, Jurkat Cells, Mitogen-Activated Protein Kinases metabolism, Phosphorylation, Receptors, Antigen, T-Cell metabolism, Signal Transduction, T-Lymphocytes enzymology, Transcriptional Activation genetics, ZAP-70 Protein-Tyrosine Kinase, Interleukin-2 metabolism, Phosphoproteins metabolism, Protein-Tyrosine Kinases metabolism, T-Lymphocytes metabolism
- Abstract
Rlk/Txk is a T-cell-specific member of the Btk/Tec family of tyrosine kinases, whereas SLP-76 is a lymphoid adaptor that is essential for pre-TcR and mature TcR signaling. Although Rlk deficient T-cells show partial defects in T-cell proliferation, Rlk can complement ITK-/- cells with multiple defects in TcR initiated early events and interleukin (IL)-2 production. A key question is the nature of the target of Rlk responsible for bridging the TcR with the activation of IL-2 transcription. In this study, we identify a pathway in which Rlk phosphorylates SLP-76 leading to the phosphorylation of PLCgamma1, activation of ERKs, and the synergistic up-regulation of TcR-driven IL-2 NFAT/AP-1 transcription. Rlk phosphorylated the N-terminal region of SLP-76, a region that has been previously shown to serve as a target for ZAP-70. Loss of N-terminal YESP/YEPP sites of SLP-76 or the Rlk kinase activity attenuated cooperativity between Rlk and SLP-76. These observations support a model where the TcR can utilize Rlk (as well as ZAP-70) in the phosphorylation of key sites in SLP-76 leading to the up-regulation of Th1 preferred cytokine IL-2.
- Published
- 2000
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