Chen M, She H, Davis E M, Spicer C M, Kim L, Ren R, Le Beau M M, Li W
Department of Biochemistry and Molecular Biology, the Department of Medicine, the University of Chicago, Chicago, Illinois 60637, USA.
J Biol Chem. 1998 Sep 25;273(39):25171-8. doi: 10.1074/jbc.273.39.25171.
Already a dozen molecules share binding to the Src homology (SH) 3 domains of human Nck, an SH3-SH3-SH3-SH2 adapter protein. We reason that there may be multiple gene members of Nck to accommodate the large binding repertoires. Here we report identification of novel human and mouse Nck genes and rename them as the Nckalpha and Nckbeta genes (including the human Nckalpha, human Nckbeta, mouse Nckalpha, and mouse Nckbeta genes). Nckalpha and Nckbeta share 68% amino acid identity, whereas the two Nckalpha and two Nckbeta across the species show 96% identity to each other. The human Nckbeta gene is mapped to 2q12, whereas the human Nckalpha gene has previously been mapped at 3q21. Antibodies specifically against Nckalpha and Nckbeta detect Nckalpha and Nckbeta with an identical molecular mass in the same cells of various origins. Ectopically expressed Nckbeta, but not its SH2 domain mutant, strongly inhibits epidermal growth factor- and platelet-derived growth factor-stimulated DNA synthesis. Consistently, epidermal growth factor receptor and platelet-derived growth factor receptor preferentially interact with Nckbeta over Nckalpha in vitro. This study indicates that Nck is a multiple gene family and that each gene may have its own signaling specificity. Because previous anti-Nck (human Nckalpha) antibodies cross-react with Nckbeta, reassessment of those studies with specific Nck genes would be necessary.
已经有十几种分子与人类Nck的Src同源（SH）3结构域结合，Nck是一种SH3-SH3-SH3-SH2衔接蛋白。我们推测可能存在多个Nck基因成员来容纳大量的结合谱。在此，我们报告了新型人类和小鼠Nck基因的鉴定，并将它们重新命名为Nckalpha和Nckbeta基因（包括人类Nckalpha、人类Nckbeta、小鼠Nckalpha和小鼠Nckbeta基因）。Nckalpha和Nckbeta的氨基酸同一性为68%，而跨物种的两个Nckalpha和两个Nckbeta彼此间的同一性为96%。人类Nckbeta基因定位于2q12，而人类Nckalpha基因先前已定位于3q21。特异性针对Nckalpha和Nckbeta的抗体在各种来源的相同细胞中检测到分子量相同的Nckalpha和Nckbeta。异位表达的Nckbeta，而不是其SH2结构域突变体，强烈抑制表皮生长因子和血小板衍生生长因子刺激的DNA合成。一致地，表皮生长因子受体和血小板衍生生长因子受体在体外与Nckbeta的相互作用优先于Nckalpha。这项研究表明Nck是一个多基因家族，并且每个基因可能具有其自身的信号特异性。由于先前的抗Nck（人类Nckalpha）抗体与Nckbeta发生交叉反应，因此有必要用特定的Nck基因对那些研究进行重新评估。
