• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Identification of Src, Fyn, and Lyn SH3-binding proteins: implications for a function of SH3 domains.
【24h】

Identification of Src, Fyn, and Lyn SH3-binding proteins: implications for a function of SH3 domains.

机译：Src，Fyn和Lyn SH3结合蛋白的鉴定：对SH3域功能的影响。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Src homology 3 (SH3) domains mediate protein-protein interactions necessary for the coupling of cellular proteins involved in intracellular signal transduction. We previously established solution-binding conditions that allow affinity isolation of Src SH3-binding proteins from cellular extracts (Z. Weng, J. A. Taylor, C. E. Turner, J. S. Brugge, and C. Seidel-Dugan, J. Biol. Chem. 268:14956-14963, 1993). In this report, we identified three of these proteins: Shc, a signaling protein that couples membrane tyrosine kinases with Ras; p62, a protein which can bind to p21rasGAP; and heterogeneous nuclear ribonucleoprotein K, a pre-mRNA-binding protein. All of these proteins contain proline-rich peptide motifs that could serve as SH3 domain ligands, and the binding of these proteins to the Src SH3 domain was inhibited with a proline-rich Src SH3 peptide ligand. These three proteins, as well as most of the other Src SH3 ligands, also bound to the SH3 domains of the closely related protein tyrosine kinases Fyn and Lyn. However, Src- and Lyn-specific SH3-binding proteins were also detected, suggesting subtle differences in the binding specificity of the SH3 domains from these related proteins. Several Src SH3-binding proteins were phosphorylated in Src-transformed cells. The phosphorylation of these proteins was not detected in cells transformed by a mutant variant of Src lacking the SH3 domain, while there was little change in tyrosine phosphorylation of other Src-induced phosphoproteins. In addition, the coprecipitation of v-Src with two tyrosyl-phosphorylated proteins with M(r)s of 62,000 and 130,000 was inhibited by incubation with a Src SH3 peptide ligand, suggesting that the binding of these substrate proteins is dependent on interactions with the SH3 domain. These results strongly suggest a role for the Src SH3 domain in the recruitment of substrates to this protein tyrosine kinase, either through direct interaction with the SH3 domain or indirectly through interactions with proteins that bind to the SH3 domain.
机译：Src同源性3（SH3）域介导耦合细胞内信号转导的细胞蛋白所必需的蛋白-蛋白相互作用。我们先前建立了溶液结合条件，可以从细胞提取物中亲和分离Src SH3结合蛋白（Z.Weng，JA Taylor，CE Turner，JS Brugge和C.Seidel-Dugan，J.Biol.Chem.268：14956 -14963，1993）。在本报告中，我们鉴定了其中三种蛋白：Shc，一种将膜酪氨酸激酶与Ras偶联的信号蛋白; p62，一种可与p21rasGAP结合的蛋白质;以及异源核糖核蛋白K（一种mRNA前结合蛋白）。所有这些蛋白质均含有可以用作SH3结构域配体的富含脯氨酸的肽基序，并且这些蛋白质与Src SH3结构域的结合被富含脯氨酸的Src SH3肽配体所抑制。这三种蛋白质以及大多数其他Src SH3配体也与密切相关的蛋白质酪氨酸激酶Fyn和Lyn的SH3结构域结合。但是，还检测到Src和Lyn特异性的SH3结合蛋白，表明这些相关蛋白在SH3结构域的结合特异性方面存在细微差异。几种Src SH3结合蛋白在Src转化的细胞中被磷酸化。在缺少SH3结构域的Src突变变体转化的细胞中未检测到这些蛋白的磷酸化，而其他Src诱导的磷酸蛋白的酪氨酸磷酸化变化很小。此外，通过与Src SH3肽配体孵育可抑制v-Src与两个酪氨酸磷酸化蛋白的M（r）分别为62,000和130,000的共沉淀，这表明这些底物蛋白的结合取决于与Src SH3肽的相互作用。 SH3域。这些结果强烈暗示了通过与SH3结构域的直接相互作用或通过与与SH3结构域结合的蛋白的间接相互作用，Src SH3结构域在该蛋白酪氨酸激酶的底物募集中的作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号