CORRELATIONS AMONG TYROSINE PHOSPHORYLATION OF SHC, P72(SYK), PLC-GAMMA-1, AND [CA2-GAMMA-RIIA SIGNALING(](I) FLUX IN FC)

Tyrosine phosphorylation plays a critical role in Fc gamma RIIA signal ing. In a mouse macrophage cell line transfected with human Fc gamma R IIA, cross-linking Fc gamma RIIA led to the transient generation of in ositol 1, 4, 5-trisphosphate (IP3), [Ca2+](i) flux, and rapid tyrosine phosphorylation of cellular substrates, including Shc, PLC-gamma 1, a nd a tyrosine kinase p72(syk). In addition, tyrosine phosphorylated Fc gamma RIIA was co-precipitated with activated PLC-gamma 1. In contras t, no tyrosine phosphorylation of She or PLC-gamma 1 was detected in c ells transfected with mutant receptors that failed to trigger [Ca2+](i ) flux. PMA inhibits both tyrosine phosphorylation of Shc and IP3 prod uction leading to [Ca2+](i) flux. However, PMA does not affect tyrosin e phosphorylation of PLC-gamma 1 and p72(syk). These results suggest t hat tyrosine phosphorylation of Shc and PLC-gamma 1 is important for t he initiation of [Ca2+](i) flux, and that activation of protein kinase C may modulate the activity of PLC-gamma 1 through serine/threonine p hosphorylation.