Effect of genistein, a tyrosine-specific protein kinase inhibitor, on cell rounding by pH upshifting.

Cell rounding is generally regarded as a cytoskeletal change exemplified by the mitotic state of monolayer cell cultures in which mitosis-specific phosphorylation was recently cited as the molecular mechanism. Mechanistically, there appears a convergence with earlier suggestions of tyrosyl phosphorylation of cytoskeletal elements in growth-factor-induced rounding inasmuch as protein tyrosine kinase plays a major regulatory role in cell cycle progression. On the other hand, despite the permissive association between cell activation and intracellular alkalinization, inducing rounding via pH upshifts in the presence of even high concentrations (135 micrograms/ml) of a tyrosine specific protein kinase inhibitor, genistein, did not suppress the rounding response, although a distinct difference in phosphotyrosine level was demonstrated by monoclonal antiphosphotyrosine antibodies.