Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. STKE, 24 April 2007
Vol. 2007, Issue 383, p. tw145
[DOI: 10.1126/stke.3832007tw145]

EDITORS' CHOICE

Kinases Giving ITK the SLP

John F. Foley

Science’s STKE, AAAS, Washington, DC 20005, USA

Tyrosine phosphorylation and activation of phospholipase C-{gamma} (PLC-{gamma}) after stimulation of the T cell antigen receptor (TCR) is dependent on the activities of the tyrosine kinases Lck, ZAP-70 ({zeta} chain-associated protein kinase of 70 kD), and ITK (IL-2-inducible T cell kinase). Other important components are adaptor molecules, such as SLP-76 (SH2-domain-containing leukocyte protein of 76 kD), which couple Syk family kinases, such as ZAP-70, to PLC-{gamma} activation. Two tyrosine residues important for TCR-mediated phosphorylation and activation of PLC-{gamma}1 are Y783 and Y775. Although previous studies suggest that ZAP-70 and ITK act together to activate PLC-{gamma}1, it is not known which is responsible for phosphorylating the critical tyrosines. Bogin et al. performed studies in a SLP-76-deficient T cell line called J14 (derived from the human CD4+ T cell line, Jurkat) to answer this question. In vitro kinase assays with ITK, but not ZAP-70, immunoprecipitated from TCR-stimulated J14 cells (transfected with a tagged form of SLP-76) resulted in the phosphorylation of both Y783 and Y775 in a recombinant form of PLC-{gamma}1, whereas both kinases could phosphorylate SLP-76. The ability of ITK to phosphorylate PLC-{gamma}1 was dependent on SLP-76. Studies with mutants of SLP-76 found that ITK phosphorylation of recombinant PLC-{gamma}1 was dependent on the presence of tyrosines in the N-terminal region of SLP-76. Coimmunoprecipitation studies revealed that stimulation of the TCR resulted in the association of SLP-76 with ITK in J14 cells. Immunoprecipitated ITK in complex with SLP-76 was catalytically more active than uncomplexed ITK. These data suggest that SLP-76 is necessary to initiate and maintain the activity of ITK.

Y. Bogin, C. Ainey, D. Beach, D. Yablonski, SLP-76 mediates and maintains activation of the Tec family kinase ITK via the T cell antigen receptor-induced association between SLP-76 and ITK. Proc. Natl. Acad. Sci. U.S.A. 104, 6638-6643 (2007). [Abstract] [Full Text]

Citation: J. F. Foley, Giving ITK the SLP. Sci. STKE 2007, tw145 (2007).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882