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Uncoupling of Nonreceptor Tyrosine Kinases from PLC-γ1 in an SLP-76-Deficient T Cell

Science  17 Jul 1998:
Vol. 281, Issue 5375, pp. 413-416
DOI: 10.1126/science.281.5375.413

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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-γ1 (PLC-γ1), 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.

  • * To whom correspondence should be addressed. E-mail: aweiss{at}itsa.ucsf.edu

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