THE ROLE OF PROTEIN-TYROSINE PHOSPHATASES IN DENSITY-DEPENDENT GROWTH-CONTROL OF NORMAL RAT-KIDNEY CELLS

In normal rat kidney cells protein tyrosine phosphatases (PTPases) pla y a role in attaining density-dependent growth arrest after stimulatio n with mitogens. The PTPase inhibitor sodium orthovanadate prevents de nsity-dependent growth inhibition of EGF-treated cells and mimicks in that respect the action of TGFbeta and retinoic acid. However, enhance d PTPase activity is not obligatory for maintaining cells in a density -arrested state. In contrast to TGFbeta and retinoic acid, vanadate is unable to restimulate density-inhibited cells, indicating that differ ent mechanisms are operating. Yet, vanadate is strongly potentiating t he effect of low concentrations of TGFbeta but not of retinoic acid, i mplicating that tyrosine phosphorylation is linked to TGFbeta action a nd that PTPase may represent a negative control element in the TGFbeta signaling pathway.