THE P21(RAS) FARNESYLTRANSFERASE ALPHA-SUBUNIT IN TGF-BETA AND ACTIVIN SIGNALING

The alpha subunit of p21(RAS) farnesyltransferase (FNTA), which is als o shared by geranylgeranyltransferase, was isolated as a specific cyto plasmic interactor of the transforming growth factor-beta (TGF-beta) a nd activin type I receptors with the use of the yeast two-hybrid syste m. FNTA interacts specifically with ligand-free TGF-beta type I recept or but is phosphorylated and released upon ligand binding. Furthermore , the release is dependent on the kinase activity of the TGF-beta type II receptor. Thus, the growth inhibitory and differentiative pathways activated by TGF-beta and activin involve novel mechanisms of serine- threonine receptor phosphorylation-dependent release of cytoplasmic in teractors and regulation of the activation of small G proteins, such a s p21(RAS).