SPECIFIC MOTIFS RECOGNIZED BY THE SH2 DOMAINS OF CSK, 3BP2, FPS FES, GRB-2, HCP, SHC, SYK, AND VAV
SPECIFIC MOTIFS RECOGNIZED BY THE SH2 DOMAINS OF CSK, 3BP2, FPS FES, GRB-2, HCP, SHC, SYK, AND VAV
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DOI：
10.1128/mcb.14.4.2777
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发表时间：
1994-04-01
影响因子：
5.3
通讯作者：
CANTLEY, LC
中科院分区：
文献类型：
--
作者：
SONGYANG, Z;SHOELSON, SE;CANTLEY, LC
Src同源性2（SH 2）结构域通过与特定的含磷酸酪氨酸（磷酸-Tyr）序列结合而提供对细胞内信号传导的特异性。我们最近开发了一种使用简并磷酸肽文库来预测单个SH 2结构域（src家族成员、Abl、Nck、Sem 5、磷脂酶C-γ、磷脂酰肌醇-3-激酶的p85亚基和SHPTP 2（Z. Songyang、S. E. Shoelson，M. Chaudhuri湾Gish，T. Pawson，W. G. Haser，F.金，T. Roberts，S.拉特诺夫斯基河J. Lechleider，B. G.尼尔河B。Birge，J. E.法哈尔多，M. M. Chou，H.花房，B。Schaffhausen和L. C. Cantley，Cell，72：767-778，1993）。我们在这里报告的最佳识别基序的SH 2结构域从GRB-2，Drk，Csk，Vav，fps/fes，SHC，Syk（羧基末端SH 2），3BP 2，和HCP（氨基末端SH 2结构域，也称为PTP 1C和SHPTP 1）。如所预测的，来自基于β D5位置处的Phe或Tyr落入组I的蛋白质的SH 2结构域（GRB-2、3BP 2、Csk、fps/fes、Syk C-末端SH 2）选择具有一般基序磷酸-Tyr-亲水（残基）-亲水（残基）-疏水（残基）的磷酸肽。SHC和HCP的SH 2结构域（在β D5位置具有Ile、Leu或Cys的III组蛋白质）选择磷酸-Tyr-疏水-Xxx-疏水的一般基序，也如预测的那样。在β D5位置具有Thr的Vav选择磷酸-Tyr-Met-Glu-Pro作为最佳基序。每个SH 2结构域选择一个独特的最佳基序，不同于先前确定的其他SH 2结构域的基序。这些基序用于预测信号蛋白中与特定含SH 2结构域蛋白相互作用的潜在位点。预计Syk SH 2结构域结合Tyr-亲水性-疏水性-Leu/Ile基序，如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。预测SHC与这些相同基序的亚组结合。从这些研究中还提出了一个结构的基础关联的Csk与Src家族成员。
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 betaD5 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, or Cys at the betaD5 position) selected the general motif phospho-Tyr-hydrophobic-Xxx-hydrophobic, also as predicted. Vav, which has a Thr at the betaD5 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 of these same motifs. A structural basis for the association of Csk with Src family members is also suggested from these studies.