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.

Abstract

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.