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Interaction of the transforming growth factor-beta type I receptor with farnesyl-protein transferase-alpha.

Kawabata M, Imamura T, Miyazono K, Engel ME, Moses HL
J Biol Chem. 1995 270 (50): 29628-31

PMID: 8530343 · DOI:10.1074/jbc.270.50.29628

Transforming growth factor-beta 1 (TGF-beta 1) is the prototype of a large family of molecules that regulate a variety of biological processes. The type I (T beta R-I) and type II (T beta R-II) receptors for TGF-beta 1 are transmembrane serine/threonine kinases, forming a heteromeric signaling complex. Recent studies have shown that T beta R-II is a constitutively active kinase and phosphorylates T beta R-I upon ligand binding, suggesting that T beta R-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 T beta R-I that mediates TGF-beta 1-specific cellular responses in the absence of ligand and T beta R-II. To investigate signaling by TGF-beta 1, we have sought to isolate proteins that interact with the cytoplasmic region of T beta R-I. One of the proteins identified was the alpha subunit of farnesyl-protein transferase (FT alpha) that modifies a series of peptides including Ras. T beta R-I specifically interacts with FT alpha in the yeast two-hybrid system. Glutathione S-transferase-T beta R-I fusion proteins bind FT alpha translated in vitro. T beta R-I also phosphorylates FT alpha. We further show that the constitutively active T beta R-I interacted with FT alpha very strongly whereas an inactive form of T beta R-I did not. These results suggest that FT alpha may be one of the substrates of the activated T beta R-I kinase.

MeSH Terms (15)

Activin Receptors, Type I Alkyl and Aryl Transferases beta-Galactosidase Glutathione Transferase 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 Recombinant Fusion Proteins Transferases

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