Cross-talk between the proto-oncogenes Met and Ron
Cross-talk between the proto-oncogenes Met and Ron
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DOI：
10.1038/sj.onc.1203620
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发表时间：
2000-06-22
期刊：
影响因子：
8
通讯作者：
Comoglio, PM
中科院分区：
文献类型：
--
作者：
Follenzi, A;Bakovic, S;Comoglio, PM
散点因子控制着一种称为“侵入性生长”的复杂遗传程序。 HGF（散射因子1）和MSP（散射因子2）与原始康涅狄格的MET和RON编码的酪氨酸激酶受体结合。使用适当的“激酶非活性”突变受体，我们表明配体诱导的MET激活会导致滚动的磷酸化和VICE VER SN。经磷酸化是直接的，因为它发生在缺乏信号传感器对接位点的MET或RON受体中。磷酸组被转移到负责激酶上调的酪氨酸磷酸化位点（MET：Y1234/Y1235和RON：Y1238/Y1239），以及产生信号传感器对接位点（MET：MET：Y1349/Y1349/Y1356和RON Y1353/Y1353/Y1360）。转磷酸化是针对受体亚科进行的，因为在Met或Ron和Erbb1，Erbb2或Trka之间未观察到它。交联实验表明，在配体诱导的二聚化之前，细胞表面上存在非共价征收复合物。具有天然性致癌的MET突变体的激酶无活性RON受体的GO表达抑制了转化的表型，这表明无效的激酶伴侣具有显着的负面作用。这些数据表明，虽然针对配体的特异性，但散点因子受体串扰并在细胞内信号传导中合作。
Scatter Factors control a complex genetic program known as 'invasive growth'. HGF (Scatter factor 1) and MSP (Scatter Factor 2) bind to tyrosine kinase receptors encoded by the proto-oncogenes MET and RON. Using the appropriate 'kinase inactive' mutant receptors, we show that ligand-induced activation of Met results in transphosphorylation of Roll, and Vice ver sn. Transphosphorylation is direct, as it occurs in Met or Ron receptors lacking the docking sites for signal transducers. Phosphate groups are transferred to the tyrosine phosphorylation sites responsible both for kinase up-regulation (Met: Y1234/Y1235 and Ron: Y1238/Y1239) and for generation of signal transducer docking sites (Met: Y1349/Y1356 and Ron Y1353/Y1360). The transphosphorylation specifically takes place for the receptor subfamily, as it is not observed between Met or Ron and ErbB1, ErbB2 or TrkA. Cross-linking experiments show that non-covalent Met-Roll complexes are present on the cell surface, before ligand-induced dimerization. Go-expression of a kinase inactive Ron receptor with naturally-occurring oncogenic Met mutants suppresses the transforming phenotype, suggesting a dominant negative role for the inefficient kinase partner. These data show that, while specific for their ligands, scatter factor receptors cross-talk and cooperate in intracellular signaling.