Letourneur O, Goetschy J F, Horisberger M, Grütter M G
Pharmaceutical Division, Ciba Geigy Ltd., Basel, Switzerland.
Biochem Biophys Res Commun. 1996 Jul 25;224(3):709-16. doi: 10.1006/bbrc.1996.1088.
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.
转化生长因子-β（TGF-β）通过介导两种不同的跨膜丝氨酸/苏氨酸激酶受体，即I型（TβRI）和II型（TβRII）的结合来传递信号。在此，我们利用重组人TβRII胞外结构域（TβRII-ED）来分析TGF-β/TβRII复合物的形成，这是构建信号复合物的初始事件。我们发现重组TβRII-ED与TGF-β3的结合效率高于TGF-β2，因此维持了天然TβRII对不同TGF-β同工型的结合选择性。生化分析表明，游离的TβRII-ED以单体形式表达。配体结合后，TGF-β3和-β2同工型均诱导TβRII-ED同源二聚化，每个TGF-β亚基能够结合一个TβRII-ED分子。这些结果表明，配体依赖性受体二聚化可能是TGF-β信号复合物形成过程中的一个重要早期步骤。
