Platelet-activating factor-induced inositol 1,4,5-trisphosphate generation in undifferentiated and differentiated U937 cells: role of tyrosine kinase.

We compared the effect of platelet-activating factor (PAF) on inositol 1,4,5-trisphosphate (IP3) content in undifferentiated and differentiated U937 cells. In both cell types, PAF induced a rapid transient and concentration-dependent elevation of IP3 content. The production of IP3 in response to PAF was greater in differentiated than in undifferentiated cells. The increases in IP3 produced by PAF in both types of cell were inhibited by the PAF receptor antagonist, WEB 2086, as well as by the tyrosine kinase inhibitor, genistein. PAF also caused increased tyrosine phosphorylation of a 32 kDa protein substrate in both undifferentiated and differentiated cells. The magnitude of the phosphorylation was, however, greater in the differentiated cells. Genistein reduced the PAF-induced tyrosine phosphorylation of the substrate in both cell preparations. The specific binding of [3H]PAF was also markedly enhanced in differentiated cells. This effect was attenuated by genistein. The results indicate that PAF induces the production of IP3 in U937 cells via tyrosine kinase-mediated mechanisms and this process is augmented in differentiated cells.