Lammers R, Van Obberghen E, Ballotti R, Schlessinger J, Ullrich A
Max-Planck Institut für Biochemie, Martinsried, Federal Republic of Germany.
J Biol Chem. 1990 Oct 5;265(28):16886-90.
Fully functional chimeric receptors, consisting of major epidermal growth factor and insulin receptor domains, were co-expressed with kinase-negative epidermal growth factor and insulin receptor mutants in human kidney fibroblasts. Under these conditions, homologous extracellular and cytoplasmic domains mediated association of receptors and their precursors. The significance of receptor-receptor interaction was confirmed by transphosphorylation of kinase-negative receptors by ligand-activated chimeric receptors, which was observed between receptors sharing the same cytoplasmic domain as well as between receptors bearing only the same extracellular domain and containing heterologous kinases. Furthermore, the impaired ligand internalization capacity of a kinase-deficient insulin receptor was partially restored by transphosphorylation. Our experiments suggest interreceptor transphosphorylation and transactivation as a possible mechanism for signal amplification.
由主要表皮生长因子和胰岛素受体结构域组成的全功能嵌合受体，与激酶阴性的表皮生长因子和胰岛素受体突变体在人肾成纤维细胞中共同表达。在这些条件下，同源的细胞外和细胞质结构域介导了受体及其前体的缔合。通过配体激活的嵌合受体对激酶阴性受体的转磷酸化证实了受体-受体相互作用的重要性，在共享相同细胞质结构域的受体之间以及仅具有相同细胞外结构域且含有异源激酶的受体之间都观察到了这种转磷酸化。此外，激酶缺陷型胰岛素受体受损的配体内化能力通过转磷酸化得到了部分恢复。我们的实验表明受体间转磷酸化和反式激活可能是信号放大的一种机制。
