Interaction of the transforming growth factor-β type I receptor with farnesyl-protein transferase-α

Abstract

Transforming growth factor-β1 (TGF-β1) is the prototype of a large family of molecules that regulate a variety of biological processes. The type I (TβR-I) and type II (TβR-II) receptors for TGF-β1 are transmembrane serine/threonine kinases, forming a heteromeric signaling complex. Recent studies have shown that TβR-II is a constitutively active kinase and phosphorylates TβR-I upon ligand binding, suggesting that TβR-I is the effector subunit of the receptor complex, which transduces signals to intracellular targets. This model has been further confirmed by the identification of constitutively active TβR-I that mediates TGF-β1-specific cellular responses in the absence of ligand and TβR-II. To investigate signaling by TGF-β1, we have sought to isolate proteins that interact with the cytoplasmic region of TβR-I. One of the proteins identified was the α subunit of farnesyl-protein transferase (FTα) that modifies a series of peptides including Ras. TβR-I specifically interacts with FTα in the yeast two-hybrid system. Glutathione S-transferase-TβR-I fusion proteins bind FTα translated in vitro. TβR-I also phosphorylates FTα. We further show that the constitutively active TβR-I interacted with FTα very strongly whereas an inactive form of TβR-I did not. These results suggest that FTα may be one of the substrates of the activated TβR-I kinase.