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

doi:10.1074/jbc.270.50.29628

Interaction of the Transforming Growth Factor- Type I Receptor with Farnesyl-protein Transferase-(*)

From the (1) Vanderbilt Cancer Center, Nashville, Tennessee 37232-6838,
(2) Department of Biochemistry, The Cancer Institute, Tokyo, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan, and
(3) Ludwig Institute for Cancer Research, Box 595, Biomedical Center, S-751 24 Uppsala, Sweden

^§ To whom correspondence should be addressed:
Vanderbilt Cancer Center, 649 Medical Research Bldg. II, Nashville, TN 37232-6838.
Tel.: 615-936-1782; Fax: 615-936-1790.

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.

Footnotes

↵* This work was supported in part by National Institutes of Health Grant CA 42572 (to H. L. M.) and grants-in-aid from the Ministry of Education, Science and Culture of Japan (to M. K. and K. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

TGF-β

transforming growth factor-β

TβR

TGF-β receptor

FT

farnesyl transferase

ALK

activin receptor-like kinase

PCR

polymerase chain reaction

GST

glutathione S-transferase

PAGE

polyacrylamide gel electrophoresis

X-Gal

5-bromo-4-chloro-3-indoyl β-D-galactoside.
- Received September 25, 1995.
- Revision received October 17, 1995.