Xu H, Lee K W, Goldfarb M
Brookdale Center for Developmental and Molecular Biology, Cellular, Biochemical and Developmental Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.
J Biol Chem. 1998 Jul 17;273(29):17987-90. doi: 10.1074/jbc.273.29.17987.
Fibroblast growth factors (FGFs) stimulate tyrosine phosphorylation of a membrane-anchored adapter protein, FRS2/SNT-1, promoting its association with Shp-2 tyrosine phosphatase and upstream activators of Ras. Using the yeast two-hybrid protein-protein interaction assay, we show that FRS2/SNT-1 and a newly isolated SNT-2 protein directly bind to FGF receptor-1 (FGFR-1). A juxtamembrane segment of FGFR-1 and the phosphotyrosine-binding domain of SNTs are both necessary and sufficient for interaction in yeast and in vitro, and FGFR-mediated SNT tyrosine phosphorylation in vivo requires these segments of receptor and SNT. Our findings establish SNTs as direct protein links between FGFR-1 and multiple downstream pathways. The SNT binding motif of FGFR-1 is distinct from previously described phosphotyrosine-binding domain recognition motifs, lacking both tyrosine and asparagine residues.
成纤维细胞生长因子（FGFs）可刺激一种膜锚定衔接蛋白FRS2/SNT-1的酪氨酸磷酸化，促进其与Shp-2酪氨酸磷酸酶及Ras上游激活剂的结合。利用酵母双杂交蛋白质-蛋白质相互作用分析，我们发现FRS2/SNT-1和新分离出的SNT-2蛋白可直接与成纤维细胞生长因子受体-1（FGFR-1）结合。FGFR-1的近膜段和SNTs的磷酸酪氨酸结合结构域对于酵母和体外的相互作用均是必需且充分的，并且体内FGFR介导的SNT酪氨酸磷酸化需要受体和SNT的这些片段。我们的研究结果确立了SNTs作为FGFR-1与多个下游通路之间直接的蛋白质连接。FGFR-1的SNT结合基序不同于先前描述的磷酸酪氨酸结合结构域识别基序，既缺乏酪氨酸残基也缺乏天冬酰胺残基。
