The p21RAS Farnesyltransferase α Subunit in TGF-β and Activin Signaling

The alpha subunit of p21RAS farnesyltransferase (FNTA), which is also shared by geranylgeranyltransferase, was isolated as a specific cytoplasmic interactor of the transforming growth factor-β (TGF-β) and activin type I receptors with the use of the yeast two-hybrid system. FNTA interacts specifically with ligand-free TGF-β type I receptor but is phosphorylated and released upon ligand binding. Furthermore, the release is dependent on the kinase activity of the TGF-β type II receptor. Thus, the growth inhibitory and differentiative pathways activated by TGF-β and activin involve novel mechanisms of serine-threonine receptor phosphorylation-dependent release of cytoplasmic interactors and regulation of the activation of small G proteins, such as p21RAS.

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