Activation of p21^ras by transforming growth factor β in epithelial cells

The transforming growth factor β (TGFβ) family members are ubiquitously expressed and control a variety of cellular processes by interacting with at least two types of high affinity cell surface receptors. However, the primary signal transduction mechanism of the receptors is unknown. The ros-encoded 21-kDa GTP binding proteins have recently been shown to mediate the effects of other polypeptide growth factors. Here we show that both TGFβ₁ and TGFβ₂ (5 ng/ ml) result in a rapid (within 6 or 12 min, respectively) stimulation of GTP bound to p21^ras in TGFβ-sensitive intestinal epithelial cells. Further, the CCL64 epithelial cell line, extremely sensitive to growth inhibition by TGFβ, displayed a concentration-dependent increase in GTP bound to p21^ras by TGFβ₁ and a rapid activation of p21^ras by TGFβ₂. The results provide the first direct evidence for rapid activation of a receptor coupling component for TGFβ in epithelial cells.