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首页> 外文期刊>Molecular and Cellular Biology >A novel recognition motif for phosphatidylinositol 3-kinase binding mediates its association with the hepatocyte growth factor/scatter factor receptor.
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A novel recognition motif for phosphatidylinositol 3-kinase binding mediates its association with the hepatocyte growth factor/scatter factor receptor.

机译：磷脂酰肌醇3-激酶结合的新型识别基序介导其与肝细胞生长因子/散射因子受体的关联。

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摘要

The pleiotropic effects (mitogenesis, motogenesis, and morphogenesis) elicited by hepatocyte growth factor/scatter factor (HGF/SF) are mediated by the activation of the tyrosine kinase receptor encoded by the MET proto-oncogene. Following autophosphorylation, the receptor associates with the p85/110 phosphatidylinositol (PI) 3-kinase complex in vivo and in vitro. By a combination of two complementary approaches, competition with synthetic phosphopeptides and association with Tyr-Phe receptor mutants, we have identified Y-1349 and Y-1356 in the HGF/SF receptor as the binding sites for PI 3-kinase. Y-1349VHV and Y-1356VNV do not conform to the canonical consensus sequence YXXM for PI 3-kinase binding and thus define YVXV as a novel recognition motif. Y-1349 and Y-1356 are located within the C-terminal portion of the HGF/SF receptor and are phosphorylation sites. The affinity of the N- and C-terminal src homology region 2 (SH2) domains of p85 for the phosphopeptides including Y-1349 and Y-1356 is 2 orders of magnitude lower than that measured for Y-751 in the platelet-derived growth factor receptor binding site. However, the closely spaced duplication of the novel recognition motif in the native HGF/SF receptor may allow binding with both SH2 domains of p85, thus generating an efficient docking site for PI 3-kinase. In agreement with this model, we have observed that a phosphopeptide including both Y-1349 and Y-1356 activates PI 3-kinase in vitro.
机译：肝细胞生长因子/散射因子（HGF / SF）引发的多效性作用（促有丝分裂，运动发生和形态发生）是由MET原癌基因编码的酪氨酸激酶受体的激活介导的。自磷酸化后，该受体在体内和体外与p85 / 110磷脂酰肌醇（PI）3-激酶复合体缔合。通过两种互补方法的组合，与合成磷酸肽的竞争以及与Tyr-Phe受体突变体的结合，我们已经确定了HGF / SF受体中的Y-1349和Y-1356是PI 3-激酶的结合位点。 Y-1349VHV和Y-1356VNV不符合PI 3-激酶结合的规范共有序列YXXM，因此将YVXV定义为新的识别基序。 Y-1349和Y-1356位于HGF / SF受体的C端部分，是磷酸化位点。 p85的N和C端src同源区域2（SH2）域对包括Y-1349和Y-1356在内的磷酸肽的亲和力比在血小板衍生的生长中对Y-751测得的亲和力低2个数量级因子受体结合位点。但是，在天然HGF / SF受体中新识别基序的紧密间隔复制可以允许与p85的两个SH2域结合，从而为PI 3-激酶产生有效的停靠位点。与该模型一致，我们已经观察到包括Y-1349和Y-1356在内的磷酸肽在体外激活PI 3-激酶。

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