The p21$^{RAS}$ Farnesyltransferase α Subunit in TGF-β and Activin Signaling

• Published in: Science (American Association for the Advancement of Science) 1996-02, Vol.271 (5252), p.1120-1122
• Main Authors: Wang, Tongwen, Danielson, Paul D., Li, Bi-yu, Shah, Paresh C., Kim, Stephen D., Donahoe, Patricia K.
• Format: Article
• Language: English
• Subjects: Activin Receptors; Activin Receptors, Type I; Activins; Alkyl and Aryl Transferases; Amino Acid Sequence; Amino acids; Animals; Antibodies; B lymphocytes; Base Sequence; Cell Line; COS cells; Gin; Humans; Inhibins - metabolism; Libraries; Ligands; Molecular Sequence Data; Mutation; Phosphorylation; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Receptor, Transforming Growth Factor-beta Type I; Receptor, Transforming Growth Factor-beta Type II; Receptors; Receptors, Growth Factor - metabolism; Receptors, Transforming Growth Factor beta - chemistry; Receptors, Transforming Growth Factor beta - genetics; Receptors, Transforming Growth Factor beta - metabolism; Recombinant Fusion Proteins - metabolism; Signal Transduction; Transferases - metabolism; Transforming Growth Factor beta - metabolism; Yeasts
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.271.5252.1120

The α subunit of p21$^{RAS}$ farnesyltransferase (FNTA), which is also shared by geranylgeranyltransferase, was isolated as a specific cytoplasmic interactor of the transforming growth factor-β (TGF-β) and activin type I receptors with the use of the yeast two-hybrid system. FNTA interacts specifically with ligand-free TGF-β type I receptor but is phosphorylated and released upon ligand binding. Furthermore, the release is dependent on the kinase activity of the TGF-β type II receptor. Thus, the growth inhibitory and differentiative pathways activated by TGF-β and activin involve novel mechanisms of serine-threonine receptor phosphorylation-dependent release of cytoplasmic interactors and regulation of the activation of small G proteins, such as p21$^{RAS}$.