Signal transduction and TGF-beta superfamily receptors.
The TGF-beta superfamily includes a large number of related growth and differentiation factors expressed in virtually all phyla. Superfamily members bind to specific cell surface receptors that activate signal transduction mechanisms to elicit their effects. Candidate receptors fall into two primary groups, termed type I and type II receptors. Both types are serine/threonine kinases. Upon activation by the appropriate ligand, type I and type II receptors physically interact to form hetero-oligomers and subsequently activate intracellular signaling cascades, ultimately regulating gene transcription and expression. In addition, TGF-beta binds to a third receptor class, type III, a membrane-anchored proteoglycan lacking the kinase activity typical of signal transducing molecules. Type III receptors appear to regulate ligand availability to type I and type II receptors. Although a number of transduction mechanisms may be available to TGF-beta superfamily members, evidence gathered through the use of specific kinase and G-protein inhibitors and through assays measuring activation and levels of signaling intermediates suggests that at least one signaling pathway interacts with Ras and Raf proteins via a G-protein intermediate. Raf begins the cytoplasmic kinase cascade that leads to gene regulation. The myriad responses regulated by TGF-beta superfamily members makes the understanding of signal transduction mechanisms utilized by these proteins of great interest to a wide range of biological disciplines.
Kolodziejczyk
S M
SM
Department of Biology, Dalhousie University, Halifax, NS, Canada. SKOLODZI@AC.DAL.CA
Hall
B K
BK
D000818:Animals; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D018631:ras Proteins / Q000502:physiology
D018125:Receptors, Transforming Growth Factor beta; D014157:Transcription Factors; D011494:Protein Kinases; D019204:GTP-Binding Proteins; D018631:ras Proteins