The types II and III transforming growth factor-beta receptors form homo-oligomers.
Open Access
- 1 July 1994
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 126 (1), 139-154
- https://doi.org/10.1083/jcb.126.1.139
Abstract
Affinity-labeling experiments have detected hetero-oligomers of the types I, II, and III transforming growth factor beta (TGF-beta) receptors which mediate intracellular signaling by TGF-beta, but the oligomeric state of the individual receptor types remains unknown. Here we use two types of experiments to show that a major portion of the receptor types II and III forms homo-oligomers both in the absence and presence of TGF-beta. Both experiments used COS-7 cells co-transfected with combinations of these receptors carrying different epitope tags at their extracellular termini. In immunoprecipitation experiments, radiolabeled TGF-beta was bound and cross-linked to cells co-expressing two differently tagged type II receptors. Sequential immunoprecipitations using anti-epitope monoclonal antibodies showed that type II TGF-beta receptors form homo-oligomers. In cells co-expressing epitope-tagged types II and III receptors, a low level of co-precipitation of the ligand-labeled receptors was observed, indicating that some hetero-oligomers of the types II and III receptors exist in the presence of ligand. Antibody-mediated cross-linking studies based on double-labeling immunofluorescence explored co-patching of the receptors at the cell surface on live cells. In cells co-expressing two differently tagged type II receptors or two differently tagged type III receptors, forcing one receptor into micropatches by IgG induced co-patching of the receptor carrying the other tag, labeled by noncross-linking monovalent Fab'. These studies showed that homo-oligomers of the types II and III receptors exist on the cell surface in the absence or presence of TGF-beta 1 or -beta 2. In cells co-expressing types II and III receptors, the amount of heterocomplexes at the cell surface was too low to be detected in the immunofluorescence co-patching experiments, confirming that hetero-oligomers of the types II and III receptors are minor and probably transient species.Keywords
This publication has 54 references indexed in Scilit:
- Cloning of a TGF$beta; type I receptor that forms a heteromeric complex with the TGF$beta; type II receptorCell, 1993
- Molecular Characterization of Rat Transforming Growth Factor-β Type II ReceptorBiochemical and Biophysical Research Communications, 1993
- Molecular cloning and characterization of the human and porcine transforming growth factor-β type III receptorsBiochemical and Biophysical Research Communications, 1992
- Cloning and sequencing of a rat type II activin receptorFEBS Letters, 1992
- Multiple genes forXenopusactivin receptor expressed during early embryogenesisFEBS Letters, 1992
- Molecular cloning and characterization of a novel rat activin receptorBiochemical and Biophysical Research Communications, 1992
- TGF-β stimulation and inhibition of cell proliferation: New mechanistic insightsCell, 1990
- Membrane-anchored and soluble forms of betaglycan, a polymorphic proteoglycan that binds transforming growth factor-beta.The Journal of cell biology, 1989
- Lateral Diffusion of Proteins in MembranesAnnual Review of Physiology, 1987
- Sendai virus envelope glycoproteins become laterally mobile on the surface of human erythrocytes following fusionExperimental Cell Research, 1985