The Fc gamma RI receptor signals through the activation of hck and MAP kinase.

U937 cells differentiated with IFN-gamma (termed U937IF cells) were used to study Fc gamma RI signaling. IFN induces a functional Fc gamma RI receptor signaling pathway in U937 cells, leading to the activation of the respiratory burst. IFN induces the expression of the nonreceptor protein tyrosine kinase, hck, and cross-linking the Fc gamma RI receptor in U937IF cells results in the activation of hck kinase as evidenced by the three- to fivefold increased tyrosine phosphorylation of hck. In vitro kinase assays demonstrate that the specific kinase activity of hck is increased 10-fold after Fc gamma RI stimulation. hck is observed to associate with two prominent tyrosine-phosphorylated proteins, p72 and p95, after Fc gamma RI-activation. Fc gamma RI cross-linking also results in mobility shift in MAP kinase in U937IF cells, suggesting that the Fc gamma RI receptor signals through the activation of MAP kinase. The data suggest that hck, p72, p95, and MAP kinase are involved in signal transduction through the Fc gamma RI receptor.