TYROSINE PHOSPHORYLATION OF PHOSPHOLIPASE C-GAMMA-1 INDUCED BY CROSS-LINKING OF THE HIGH-AFFINITY OR LOW-AFFINITY FC RECEPTOR FOR IGG IN U937 CELLS

The human monocytic cell line U937 possesses two classes of the IgG Fc receptor (Fc-gamma-R), a high-affinity 72-kDa Fc-gamma-R (Fc-gamma-RI) and a low-affinity 40-kDa Fc-gamma-R (Fc-gamma-RII). Cross-linking of either class of Fc-gamma-R in U937 cells elicits an increase in the concentration of free intracellular Ca2+. A rapid rise in the concentration of inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) and of several other inositol phosphates derived from Ins-1,4,5-P3 was observed after cross-linking of Fc-gamma-Rs in U937 cells. This result suggests that Ins-1,4,5-P3, generated by the action of phospholipase C (PLC), acts as a second messenger by which Fc-gamma-Rs mobilize intracellular Ca2+ in U937 cells. The mechanism by which the cross-linking of Fc-gamma-Rs triggers activation of PLC was studied. Cross-linking of Fc-gamma-RI or Fc-gamma-RII resulted in a rapid and transient phosphorylation of PLC-gamma-1 on tyrosine residues. It has previously been shown that phosphorylation of PLC-gamma-1 on tyrosine residues activates its enzymatic activity in cells. prior incubation of U937 cells with a protein tyrosine kinase inhibitor, herbimycin A, prevented the tyrosine phosphorylation of PLC-gamma-1 and the hydrolysis of phosphatidylinositol 4,5-bisphosphate induced by the cross-linking of Fc-gamma-Rs. Thus, Fc-gamma-RI and Fc-gamma-RII appear to be functionally coupled to a nonreceptor tyrosine kinase that phosphorylates PLC-gamma-1 after receptor cross-linking, thereby causing activation of PLC-gamma-1.