Phorbol esters induce insulin receptor phosphorylation in transfected fibroblasts without affecting tyrosine kinase activity.

The effects of phorbol ester induced activation of protein kinase C on insulin receptor phosphorylation and tyrosine kinase activity have been investigated in transfected fibroblasts expressing high levels of the human insulin receptor. Receptor phosphorylation was stimulated more than two-fold over basal levels upon treating CHO.T cells with PMA. This phosphorylation was additive with, rather than antagonistic to, that induced by insulin. Furthermore, PMA treatment was completely without effect on insulin-stimulated receptor tyrosine kinase activity. Similar results were obtained in NIH3T3 HIR3.5 and Rat 1 HIRc-B cells. It is concluded that the previously reported inhibitory effect of PMA on receptor kinase activity is not of general regulatory significance in all cell types.