The transforming growth factor beta receptors types I, II, and III form hetero-oligomeric complexes in the presence of ligand.
Transforming growth factors beta (TGF-beta s) are disulfide-linked dimers. In Rat-1 cells both radioiodinated TGF-beta 1 and -beta 2 bind to and can be chemically cross-linked to type I and II receptors (which are thought to mediate effects of cell growth suppression and gene activation), to type III proteoglycan receptors, and to a novel approximately 50-kDa protein. After detergent solubilization of cells that were cross-linked with radioiodinated TGF-beta, antibodies specific for the type II receptor precipitated labeled receptor types I and III as well as type II. In these cells, the type III receptor is the predominant TGF-beta-binding protein, and antibodies specific for it precipitate mainly this cross-linked receptor. Thus, in the presence of TGF-beta ligand, receptor types II and III and types II and I form heteromeric complexes. The majority of the type III receptor does not associate with receptor types I and II, probably reflecting the relative amounts of the three receptors on the surface of Rat-1 cells. Since TGF-beta 1 but not TGF-beta 2 binds to the exoplasmic domain of the type II receptor in the absence of the type III receptor, and since both TGF-beta 1 and -beta 2 bind with high affinity to the type III receptor, we suggest that TGF-beta 2, and possibly TGF-beta 1, bind initially to the type III receptor. The TGF-beta 2-type III receptor complex would then interact with a type II receptor, thus modulating the affinity of the type II receptor for TGF-beta 2.
Moustakas
A
A
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
Lin
H Y
HY
Henis
Y I
YI
Plamondon
J
J
O'Connor-McCourt
M D
MD
Lodish
H F
HF
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001345:Autoradiography; D002460:Cell Line; D003432:Cross-Linking Reagents; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000032:analysis; D006801:Humans; D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000276:immunology; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000302:isolation & purification / Q000378:metabolism*
D000906:Antibodies; D003432:Cross-Linking Reagents; D000939:Epitopes; D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D010455:Peptides; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta