An emerging complexity of receptors for transforming growth factor-beta.
Transforming growth factor-beta (TGF-beta) is a multifunctional protein that modulates cell proliferation and interaction with the extracellular matrix. Three common TGF-beta receptors are found on the cell surface. The type III receptor is a transmembrane proteoglycan with a short cytoplasmic domain and is thought not to be involved in TGF-beta induced signalling. In contrast, the type II and type I receptors are transmembrane serine/threonine kinases. The type II receptor determines the ligand specificity, whereas the type I receptor interacts with the type II receptor and may not have a ligand binding specificity by itself. Both type II and type I receptors are involved in TGF-beta induced signalling. The type II receptor, likely in conjunction with the type I receptor, is required for the antiproliferative effect of TGF-beta, whereas the type I receptor is the likely mediator of the effects of TGF-beta on the expression of several genes including some extracellular matrix proteins. To address the role of TGF-beta signalling in myoblast differentiation, we transfected a dominant negative mutant of the type II receptor in myoblasts, thus inhibiting type II receptor mediated signalling. These cells not longer had the ability to differentiate in vitro or in vivo, suggesting that TGF-beta signalling through the type II receptor provides competence for myoblastic differentiation. These studies also indicate that there are several signalling pathways involved in myoblastic differentiation, one of which is modulated by the TGF-beta signalling.
Derynck
R
R
Dept. of Growth and Development, University of California at San Francisco 94143-0640, USA.
Chen
R H
RH
Ebner
R
R
Filvaroff
E H
EH
Lawler
S
S
D030201:Activin Receptors, Type I; D000818:Animals; D002454:Cell Differentiation; D005314:Embryonic and Fetal Development; D006801:Humans; D051379:Mice; D009024:Morphogenesis; D005810:Multigene Family; D009132:Muscles / Q000166:cytology / Q000196:embryology; D009363:Neoplasm Proteins / Q000502:physiology; D009928:Organ Specificity; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011509:Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000145:classification* / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013329:Structure-Activity Relationship; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
D009363:Neoplasm Proteins; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C071736:betaglycan; D020794:Receptor Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II