UNCOUPLING OF NONRECEPTOR TYROSINE KINASES FROM PLC-GAMMA-1 IN AN SLP-76-DEFICIENT T-CELL

Activation of nonreceptor protein tyrosine kinases (PTKs) is essential for T cell receptor (TCR) responsiveness; however, the function of in dividual PTK substrates is often uncertain. A mutant T cell Line was i solated that Lacked expression of SLP-76 (SH2 domain-containing Leukoc yte protein of 76 kilodaltons), a hematopoietically expressed adaptor protein and PTK substrate. SLP-76 was not required for TCR-induced tyr osine phosphorylation of most proteins, but was required for optimal t yrosine phosphorylation and activation of phospholipase C-gamma l (PLC -gamma l), as well as Ras pathway activation. TCR-inducible gene expre ssion was dependent on SLP-76. Thus, coupling of TCR-regulated PTKs to downstream signaling pathways requires SLP-76.