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首页> 外文期刊>Molecular and Cellular Biology >Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav.
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Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav.

机译：由Csk，3BP2，fps / fes，GRB-2，HCP，SHC，Syk和Vav的SH2域识别的特定基序。

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Src homology 2 (SH2) domains provide specificity to intracellular signaling by binding to specific phosphotyrosine (phospho-Tyr)-containing sequences. We recently developed a technique using a degenerate phosphopeptide library to predict the specificity of individual SH2 domains (src family members, Abl, Nck, Sem5, phospholipase C-gamma, p85 subunit of phosphatidylinositol-3-kinase, and SHPTP2 (Z. Songyang, S. E. Shoelson, M. Chaudhuri, G. Gish, T. Pawson, W. G. Haser, F. King, T. Roberts, S. Ratnofsky, R. J. Lechleider, B. G. Neel, R. B. Birge, J. E. Fajardo, M. M. Chou, H. Hanafusa, B. Schaffhausen, and L. C. Cantley, Cell 72:767-778, 1993). We report here the optimal recognition motifs for SH2 domains from GRB-2, Drk, Csk, Vav, fps/fes, SHC, Syk (carboxy-terminal SH2), 3BP2, and HCP (amino-terminal SH2 domain, also called PTP1C and SHPTP1). As predicted, SH2 domains from proteins that fall into group I on the basis of a Phe or Tyr at the beta D5 position (GRB-2, 3BP2, Csk, fps/fes, Syk C-terminal SH2) select phosphopeptides with the general motif phospho-Tyr-hydrophilic (residue)-hydrophilic (residue)-hydrophobic (residue). The SH2 domains of SHC and HCP (group III proteins with Ile, Leu, of Cys at the beta D5 position) selected the general motif phospho-Tyr-hydrophobic-Xxx-hydrophobic, also as predicted. Vav, which has a Thr at the beta D5 position, selected phospho-Tyr-Met-Glu-Pro as the optimal motif. Each SH2 domain selected a unique optimal motif distinct from motifs previously determined for other SH2 domains. These motifs are used to predict potential sites in signaling proteins for interaction with specific SH2 domain-containing proteins. The Syk SH2 domain is predicted to bind to Tyr-hydrophilic-hydrophilic-Leu/Ile motifs like those repeated at 10-residue intervals in T- and B-cell receptor-associated proteins. SHC is predicted to bind to a subgroup og these same motifs. A structural basis for the association of Csk with Src family members is also suggested from these studies.
机译：Src同源2（SH2）域通过结合特定的含磷酸酪氨酸（phospho-Tyr）的序列，为细胞内信号传导提供特异性。我们最近开发了一种利用简并的磷酸肽库预测单个SH2域（src家族成员，Abl，Nck，Sem5，磷脂酶C-γ，磷脂酰肌醇-3-激酶p85亚基和SHPTP2（Z. Songyang， SE Shoelson，M。Chaudhuri，G。Gish，T。Pawson，WG Haser，F。King，T。Roberts，S。Ratnofsky，RJ Lechleider，BG Neel，RB Birge，JE Fajardo，MM Chou，H。Hanafusa，B （Schaffhausen，and LC Cantley，Cell 72：767-778，1993）。我们在此报告了GRB-2，Drk，Csk，Vav，fps / fes，SHC，Syk（羧基末端SH2）的SH2域的最佳识别基序），3BP2和HCP（氨基末端SH2结构域，也称为PTP1C和SHPTP1）。正如预测的那样，来自蛋白质的SH2结构域根据在βD5位置的Phe或Tyr进入I组（GRB-2， 3BP2，Csk，fps / fes，Syk C末端SH2）选择具有以下基序的磷酸肽：Tyr-亲水（残基）-亲水（残基）-疏水（残基）。 SHC和HCP的2个域（βD5位置的Cys的Ile，Leu和Ile，Leu的III类蛋白质）也选择了一般的基序磷酸-Tyr-疏水-Xxx-疏水。在βD5位置具有Thr的Vav选择磷酸Tyr-Met-Glu-Pro作为最佳基序。每个SH2域都选择了一个独特的最佳主题，该主题不同于先前为其他SH2域确定的主题。这些基序用于预测信号蛋白中与特定的含SH2结构域蛋白相互作用的潜在位点。预计Syk SH2结构域将与Tyr-亲水-亲水-Leu / Ile基序结合，就像在T细胞和B细胞受体相关蛋白中以10个残基间隔重复的基序一样。预测SHC将结合这些相同基序的亚组。这些研究还提出了Csk与Src家族成员之间联系的结构基础。

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