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) play a role in attaining density-dependent growth arrest after stimulation with mitogens. The PTPase inhibitor sodium orthovanadate prevents density-dependent growth inhibition of EGF-treated cells and mimicks in that respect the action of TGFβ and retinoic acid. However, enhanced PTPase activity is not obligatory for maintaining cells in a density-arrested state. In contrast to TGFβ and retinoic acid, vanadate is unable to restimulate density-inhibited cells, indicating that different mechanisms are operating. Yet, vanadate is strongly potentiating the effect of low concentrations of TGFβ but not of retinoic acid, implicating that tyrosine phosphorylation is linked to TGFβ action and that PTPase may represent a negative control element in the TGFβ signaling pathway.