Cooperative binding of transforming growth factor (TGF)-beta 2 to the types I and II TGF-beta receptors.
TGF-beta 1 binds with high affinity (KD = 25-50 pM) directly to the TGF-beta type II receptor serine-threonine kinase (T beta-RII) in the absence of expression of the TGF-beta type I or III receptors (T beta-RI and T beta-RIII). The serine-threonine kinase T beta-RI is essential for TGF-beta 1 signaling but not for binding to T beta-RII. TGF-beta 2, in contrast, does not bind directly to T beta-RII, although coexpression of T beta-RIII does allow binding and cross-linking of TGF-beta 2 to T beta-RII. Here we show that in transfected COS cells binding and cross-linking of 125I-TGF-beta 2 to T beta-RI or T beta-RII requires expression of both receptors. In cells transfected with the c-myc-tagged human T beta-RII cDNA, only low amounts of 125I-TGF-beta 2 cross-linked to T beta-RI and T beta-RII were detected even with high concentrations (700 pM) of ligand. Cotransfection of the influenza-hemagglutinin-tagged human T beta-RI cDNA dramatically increased the binding of TGF-beta 2 to T beta-RII; the concentration of 125I-TGF-beta 2 required for half-maximal binding and cross-linking to T beta-RI and T beta-RII was approximately 40 pM. Coimmunoprecipitation studies showed that the high affinity receptor for TGF-beta 2 is composed of a hetero-oligomer of T beta-RI and T beta-RII. Thus TGF-beta 1 and -beta 2 bind to TGF-beta receptors in different ways; TGF-beta 1 binds directly to T beta-RII, while binding of TGF-beta 2 to T beta-RII requires coexpression of T beta-RI or T beta-RIII.
Rodriguez
C
C
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Chen
F
F
Weinberg
R A
RA
Lodish
H F
HF
D030201:Activin Receptors, Type I; D000818:Animals; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D006801:Humans; D011233:Precipitin Tests; D011485:Protein Binding; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D003432:Cross-Linking Reagents; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; 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