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 tile 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.