TGF-beta signaling from a three-dimensional perspective: insight into selection of partners.
Members of the transforming growth factor beta (TGF-beta) family, which include TGF-beta s, activins and bone morphogenetic proteins (BMPs), are potent regulators of cell proliferation, differentiation, migration and apoptosis. They act through binding to and activating serine/threonine kinase receptors on the cell surface and triggering intracellular signaling pathways in which Smad proteins have essential roles. Here, we discuss recent structure-based studies of TGF-beta s and BMPs, their receptors, and of Smad proteins, which have unravelled insights into ligand specificity, receptor and Smad activation, as well as new features of Smads as phosphoserine-binding entities.
Souchelnytskyi
Serhiy
S
Ludwig Institute for Cancer Research, Box 595, Husargatan 3, SE-751 24, Uppsala, Sweden. Serhiy.Souchelnytskyi@licr.uu.se
Moustakas
Aristidis
A
Heldin
Carl-Henrik
CH
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000737:chemistry / Q000502:physiology; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D015398:Signal Transduction; D051785:Smad Proteins; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D051785:Smad Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta