INHIBITION OF EPIDERMAL GROWTH FACTOR-DEPENDENT PROTEIN-TYROSINE PHOSPHORYLATION BY PHORBOL-MYRISTATE ACETATE IS MEDIATED BY PROTEIN-TYROSINE-PHOSPHATASE ACTIVITY

Incubation of HER14 cells with phorbol myristate acetate (PMA) decreas es epidermal growth factor (EGF)-dependent protein tyrosine phosphoryl ation, except for a 40-kDa MAP kinase II-like protein, whose tyrosine phosphorylation is further enhanced. The inhibitory effect of PMA on E GF-dependent protein tyrosine phosphorylation is reversed if cells are pre-incubated with a combination of Na-3,VO4, and NaF, two known inhi bitors of protein tyrosine phosphatase activity. Protein tyrosine phos phatase activity of cell homogenate was measured on immunopurified EGF receptor, and was found to be enhanced in PMA-treated cells. These da ta suggest that the inhibitory effect of PMA on EGF-dependent protein tyrosine phosphorylation in HER14 cells may be mediated by protein tyr osine phosphatase activity.