INVOLVEMENT OF A PHOSPHOTYROSINE PROTEIN PHOSPHATASE IN THE SUPPRESSION OF PLATELET-DERIVED GROWTH-FACTOR RECEPTOR AUTOPHOSPHORYLATION IN RAS-TRANSFORMED CELLS

The nature of the suppression of platelet-derived growth factor (PDGF) receptor autophosphorylation in ras-transformed NIH 3T3 fibroblasts w as investigated. The PDGF receptor from ras-transformed cells that had been purified by wheatgerm-lectin affinity chromatography displayed n ormal PDGF-induced autophosphorylation, indicating that the receptor i s not irreversibly modified. Various phosphotyrosine-protein-phosphata se inhibitors did not reverse the inhibition of PDGF-receptor kinase i n crude membrane preparations from ras-transformed cells. However, tre atment of intact ras-transformed cells both with 2 mM sodium orthovana date and with 20 muM phenylarsine oxide restored PDGF-receptor tyrosin e-kinase activity to a level similar to that observed in normal cells. Direct measurement of the phosphatase activities in crude cellular fr actions revealed a 2.5-fold higher membrane-associated phosphotyrosine -protein-phosphatase activity in ras-transformed cells, whereas phosph oserine-protein-phosphatase activity remained unchanged between the ce ll lines. These data suggest that the suppression of the PDGF-receptor tyrosine-kinase activity in ras-transformed cells is mediated via an inhibitory component, distinct from the receptor, that may be positive ly regulated by the dephosphorylation of tyrosine residue(s).