Interaction of transforming growth factor-β receptor I with farnesyl-protein transferase-α in yeast and mammalian cells

Transforming growth factor β (TGF-β) signals through two transmembrane serine/threonine kinases, known as TβR-I and TβR-II. Several lines of evidence suggest that TβR-II acts as a primary receptor, binding TGF-β and phosphorylating TβR-I whose kinase activity then propagates the signal to unknown substrates. We report an interaction between TβR-I and the farnesylprotein transferase-α subunit (FT-α) both in a yeast two-hybrid system and in mammalian cells. These findings raise the possibility that TGF-β might regulate cellular functions by altering the ability of FT-α to catalyze isoprenylation of targets such as G proteins, lamins, or cytoskeletal components. However, we provide evidence that TGF-β action does not alter the overall protein isoprenyl transferase activity in Mv1Lu mink lung epithelial cells. In fact, the β subunits of farnesyl transferase and geranylgeranyl transferase, which are necessary for the activity of FT-α, prevent the association of FT-α with TβR-I. Furthermore, farnesyl transferase activity is shown to be dispensable for TGF-β signaling of growth inhibitory and transcriptional responses in these cells. These results suggest that the interaction between TβR-I and FT-α does not affect the known functions of these two proteins.