Dhalluin C, Yan K S, Plotnikova O, Lee K W, Zeng L, Kuti M, Mujtaba S, Goldfarb M P, Zhou M M
Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York 10029, USA.
Mol Cell. 2000 Oct;6(4):921-9. doi: 10.1016/s1097-2765(05)00087-0.
SNT adaptor proteins transduce activation of fibroblast growth factor receptors (FGFRs) and neurotrophin receptors (TRKs) to common signaling targets. The SNT-1 phosphotyrosine binding (PTB) domain recognizes activated TRKs at a canonical NPXpY motif and, atypically, binds to nonphosphorylated FGFRs in a region lacking tyrosine or asparagine. Here, using NMR and mutational analyses, we show that the PTB domain utilizes distinct sets of amino acid residues to interact with FGFRs or TRKs in a mutually exclusive manner. The FGFR1 peptide wraps around the beta sandwich structure of the PTB domain, and its binding is possibly regulated by conformational change of a unique C-terminal beta strand in the protein. Our results suggest mechanisms by which SNTs serve as molecular switches to mediate the essential interplay between FGFR and TRK signaling during neuronal differentiation.
SNT衔接蛋白将成纤维细胞生长因子受体（FGFRs）和神经营养因子受体（TRKs）的激活信号转导至共同的信号靶点。SNT-1磷酸酪氨酸结合（PTB）结构域在一个典型的NPXpY基序处识别激活的TRKs，并且非典型地在缺乏酪氨酸或天冬酰胺的区域与非磷酸化的FGFRs结合。在这里，我们通过核磁共振（NMR）和突变分析表明，PTB结构域利用不同的氨基酸残基组以互斥的方式与FGFRs或TRKs相互作用。FGFR1肽环绕PTB结构域的β三明治结构，其结合可能受该蛋白中独特的C端β链构象变化的调节。我们的结果提示了SNTs作为分子开关在神经元分化过程中介导FGFR和TRK信号之间重要相互作用的机制。
