Formation of hetero-oligomeric complexes of type I and type II receptors for transforming growth factor-beta.
Transforming growth factor-beta (TGF-beta) transduces signals through a heteromeric complex of type I (T beta R-I) and type II (T beta R-II) TGF-beta receptors. To determine the stoichiometry of this complex we used analysis by affinity labeling with 125I-TGF-beta 1 and covalent cross-linking with disuccinimidyl suberate and immunoprecipitation using T beta R-I- or T beta R-II-specific antisera, followed by two-dimensional gel electrophoresis under nonreducing (first dimension) and reducing (second dimension) conditions. Dimers composed of T beta R-I and/or T beta R-II were observed on mink lung epithelial cells as well as COS-1 cells transfected with T beta R-I and T beta R-II cDNAs. Homodimers of T beta R-I could be demonstrated on these cells after dissociation of T beta R-II by sodium dodecyl sulfate treatment. On the cell surface of mink lung epithelial cell mutants that express only T beta R-II and do not respond to TGF-beta, and on COS-1 cells transfected with only T beta R-II, only homodimers of T beta R-II were seen. The facts that T beta R-I does not bind TGF-beta in the absence of T beta R-II and that T beta R-II forms a signaling complex with T beta R-I, together with our observations that homodimers of T beta R-I and T beta R-II are seen on responsive cells, support the notion that TGF-beta induces the formation of hetero-oligomeric receptor complexes, most likely a heterotetramer containing two molecules each of T beta R-I and T beta R-II.
Yamashita
H
H
Ludwig Institute for Cancer Research, Uppsala, Sweden.
ten Dijke
P
P
Franzén
P
P
Miyazono
K
K
Heldin
C H
CH
D000345:Affinity Labels; D000818:Animals; D002460:Cell Line; D003432:Cross-Linking Reagents; D018076:DNA, Complementary; D015180:Electrophoresis, Gel, Two-Dimensional; D008907:Mink; D008970:Molecular Weight; D011233:Precipitin Tests; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D013388:Succinimides; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000378:metabolism
D000345:Affinity Labels; D003432:Cross-Linking Reagents; D018076:DNA, Complementary; D018125:Receptors, Transforming Growth Factor beta; D013388:Succinimides; D016212:Transforming Growth Factor beta; C019358:disuccinimidyl suberate