Interaction of the Transforming Growth Factor-β Type I Receptor with Farnesyl-protein Transferase-α

• Published in: The Journal of biological chemistry 1995-12, Vol.270 (50), p.29628-29631
• Main Authors: Kawabata, Masahiro, Imamura, Takeshi, Miyazono, Kohei, Engel, Michael E., Moses, Harold L.
• Format: Article
• Language: English
• Subjects: Activin Receptors, Type I; Alkyl and Aryl Transferases; beta-Galactosidase - biosynthesis; Glutathione Transferase - biosynthesis; HeLa Cells; Humans; Kinetics; Mutagenesis, Site-Directed; Phosphorylation; Point Mutation; Protein-Serine-Threonine Kinases; Receptor, Transforming Growth Factor-beta Type I; Receptors, Transforming Growth Factor beta - biosynthesis; Receptors, Transforming Growth Factor beta - isolation & purification; Receptors, Transforming Growth Factor beta - metabolism; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - isolation & purification; Recombinant Fusion Proteins - metabolism; Transferases - biosynthesis; Transferases - isolation & purification; Transferases - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.50.29628

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.