Uncoupling of nonreceptor tyrosine kinases from PLC-gamma1 in an SLP-76-deficient T cell |
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Authors: | D Yablonski MR Kuhne T Kadlecek A Weiss |
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Affiliation: | Department of Medicine, Howard Hughes Medical Institute, Box 0795, University of California, San Francisco, San Francisco, CA 94143-0795, USA. |
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Abstract: | Activation of nonreceptor protein tyrosine kinases (PTKs) is essential for T cell receptor (TCR) responsiveness; however, the function of individual PTK substrates is often uncertain. A mutant T cell line was isolated that lacked expression of SLP-76 (SH2 domain-containing leukocyte protein of 76 kilodaltons), a hematopoietically expressed adaptor protein and PTK substrate. SLP-76 was not required for TCR-induced tyrosine phosphorylation of most proteins, but was required for optimal tyrosine phosphorylation and activation of phospholipase C-gamma1 (PLC-gamma1), as well as Ras pathway activation. TCR-inducible gene expression was dependent on SLP-76. Thus, coupling of TCR-regulated PTKs to downstream signaling pathways requires SLP-76. |
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