Subunit structure of a high-affinity receptor for type beta-transforming growth factor. Evidence for a disulfide-linked glycosylated receptor complex.
The structure of high-affinity receptors for type beta-transforming growth factor (beta TGF) has been examined by affinity labeling with 125I-beta TGF and disuccinimidyl suberate. The major receptor component labeled by 125I-beta TGF in mouse, rat, and chick fibroblasts migrated as a 280-290-kilodalton species on dodecyl sulfate-polyacrylamide electrophoresis gels in the presence of reductant, dithiothreitol. A larger (330-kilodalton) species was labeled in human fibroblasts, but comparative peptide mapping indicated a close structural relationship with receptors from mouse fibroblasts. In the absence of reductant, the affinity-labeled beta TGF receptor migrated in the gels as a larger disulfide-linked complex. The molecular mass calculated from the hydrodynamic properties of native nonreduced beta TGF receptors was 565 (mouse) or 615 kilodaltons (human). Other molecular parameters for the beta TGF receptor were: Stokes radius, 8.3-8.5 nm; sedimentation coefficient, 12.7-13.0 S; and frictional ratio, f/f0 = 1.4. The beta TGF receptor was solubilized under conditions in which the structural and ligand-binding properties of the native state were retained. beta TGF receptors solubilized from human, mouse, and chick cells interacted specifically with immobilized wheat germ agglutinin. These data suggest that the high affinity receptor for beta TGF in human, rodent, and avian fibroblasts is a disulfide-linked glycosylated 565-615-kilodalton complex with a 280-330-kilodalton subunit that contains the ligand-binding site. The oligomeric structure of the beta TGF receptor does not appear to be induced by receptor occupancy with the ligand.
Massagué
J
J
D000345:Affinity Labels / Q000378:metabolism; D000818:Animals; D002241:Carbohydrates / Q000032:analysis; D002642:Chick Embryo; D002918:Chymotrypsin / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism; D066246:ErbB Receptors; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012697:Serine Endopeptidases; D015291:Transforming Growth Factors
D000345:Affinity Labels; D002241:Carbohydrates; D004220:Disulfides; D046911:Macromolecular Substances; D010455:Peptides; D011956:Receptors, Cell Surface; D015291:Transforming Growth Factors; D066246:ErbB Receptors; D010450:Endopeptidases; D012697:Serine Endopeptidases; D002918:Chymotrypsin; C028344:glutamyl endopeptidase; D004229:Dithiothreitol