Differential effects of Cbl and 70Z/3 Cbl on T cell receptor-induced phospholipase C gamma-1 activity

We demonstrate that the differential effects Cbl and oncogenic 70Z/3 Cbl ha ve on Ca2+/Ras-sensitive NF-AT reporters is partially due to their opposing ability to regulate phospholipase C gamma 1 (PLC gamma 1) activation as de monstrated by analysis of the activation of an NF-AT reporter construct and PLC gamma 1-mediated inositol phospholipid (PI) hydrolysis. Cbl overexpres sion resulted in reduced T cell receptor-induced Pf hydrolysis, in the abse nce of any effect on PLC gamma 1 tyrosine phosphorylation, In contrast, exp ression of 70Z/3 Cbl led to an increase in basal and OKT3-induced PLC gamma 1 phosphorylation and PI hydrolysis, These data indicate that Cbl and 70Z/ 3 Cbl differentially regulate PLC gamma 1 phosphorylation and activation, T he implications of these data on the mechanism of Chi-mediated signaling re gulation are discussed. (C) 2000 Federation of European Biochemical Societi es.