Tyrphostins inhibit the epidermal growth factor receptor‐mediated breakdown of phosphoinositides

Abstract

In response to epidermal growth factor (EGF) and the Ca²⁺ ionophore A23187, the total phosphatidylinositides (IPT) increased in A431 human epidermoid carcinoma cells 1.8‐ and 2.0‐fold and in the EGF‐dependent A431/Clone 15‐2 cells 3.0‐ and 8.0‐fold, respectively, over basal levels. Both responses were inhibited by the antiproliferative agents tyrphostins, but the EGF‐induced increase in IP_T was inhibited to a much greater extent than that induced by the ionophore. Tyrphostins which are potent EGF‐receptor kinase inhibitors were also potent in blocking the EGF‐induced production of phosphoinositides. The less potent tyrphostins were found to inhibit the EGF‐dependent IP_T formation more weakly. These results support the notion that phospholipase C is activated through its phosphorylation by the EGF receptor. Tyrphostins; Epidermal growth factor; Phospholipase C phosphorylation; Ca²⁺ ionophore; (A431 cell, A431/Clone 15‐2 cell)