INHIBITION OF CELLULAR-RESPONSE TO PLATELET-DERIVED GROWTH-FACTOR BY LOW M(R) PHOSPHOTYROSINE PROTEIN PHOSPHATASE OVEREXPRESSION

The role of low M(r) phosphotyrosine protein phosphatase (PTPase) in t he control of cell proliferation was studied. A synthetic gene coding for PTPase was transfected and expressed in NIH/3T3 fibroblasts. The e ffects of the enzyme were particularly evident when cells were stimula ted by platelet-derived growth factor (PDGF). The mitogenic response t o PDGF was decreased and the inhibition reached 90%. This effect was m ore pronounced with respect to fetal calf serum stimulation. Hormone-d ependent autophosphorylation of the PDGF receptor was significantly re duced. These results demonstrate that low M(r) PTPase, a cytosolic enz yme, not only affects cellular response to PDGF but also reduces the m embrane receptor autophosphorylation.