Interaction of transforming growth factor-beta receptor I with farnesyl-protein transferase-alpha in yeast and mammalian cells.
Transforming growth factor beta (TGF-beta) signals through two transmembrane serine/threonine kinases, known as TbetaR-I and TbetaR-II. Several lines of evidence suggest that TbetaR-II acts as a primary receptor, binding TGF-beta and phosphorylating TbetaR-I whose kinase activity then propagates the signal to unknown substrates. We report an interaction between TbetaR-I and the farnesyl-protein transferase-alpha subunit (FT-alpha) both in a yeast two-hybrid system and in mammalian cells. These findings raise the possibility that TGF-beta might regulate cellular functions by altering the ability of FT-alpha to catalyze isoprenylation of targets such as G proteins, lamins, or cytoskeletal components. However, we provide evidence that TGF-beta action does not alter the overall protein isoprenyl transferase activity in Mv1Lu mink lung epithelial cells. In fact, the beta subunits of farnesyl transferase and geranylgeranyl transferase, which are necessary for the activity of FT-alpha, prevent the association of FT-alpha with TbetaR-I. Furthermore, farnesyl transferase activity is shown to be dispensable for TGF-beta signaling of growth inhibitory and transcriptional responses in these cells. These results suggest that the interaction between TbetaR-I and FT-alpha does not affect the known functions of these two proteins.
Ventura
F
F
Cell Biology and Genetics Program, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Liu
F
F
Doody
J
J
Massagué
J
J
D030201:Activin Receptors, Type I; D019883:Alkyl and Aryl Transferases; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002522:Chlorocebus aethiops; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008322:Mammals; D008969:Molecular Sequence Data; D017368:Protein Prenylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D014162:Transfection; D014166:Transferases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D046911:Macromolecular Substances; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I