Ligand-induced dimerization of the extracellular domain of the TGF-beta receptor type II.
Transforming growth factor-beta (TGF-beta) signals by mediating the association of two distinct transmembrane serine/threonine kinase receptors, the type I (T beta RI) and II (T beta RII). Here, we took advantage of recombinant human T beta RII extracellular domain (T beta RII-ED) to analyze TGF-beta/T beta RII complex formation which is the initial event in the construction of a signaling complex. We found that recombinant T beta RII-ED binds TGF-beta 3 more efficiently than TGF-beta 2 and therefore maintains the native T beta RII binding selectivity for the different TGF-beta isoforms. Biochemical analysis showed that free T beta RII-ED is expressed as a monomer. Upon ligand binding, both TGF-beta 3 and -beta 2 isoforms induce homodimerization of T beta RII-ED, each TGF-beta subunit being able to bind one T beta RII-ED molecule. These results suggested that ligand dependent receptor dimerization may be an important early step in the TGF-beta signaling complex formation.
Letourneur
O
O
Pharmaceutical Division, Ciba Geigy Ltd., Basel, Switzerland.
Goetschy
J F
JF
Horisberger
M
M
Grütter
M G
MG
D016475:3T3 Cells; D000818:Animals; D001704:Biopolymers; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006801:Humans; D007313:Insecta; D008024:Ligands; D051379:Mice; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011956:Receptors, Cell Surface / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
D001704:Biopolymers; D008024:Ligands; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II