Yamanashi Y, Baltimore D
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Cell. 1997 Jan 24;88(2):205-11. doi: 10.1016/s0092-8674(00)81841-3.
A 62 kDa protein is highly phosphorylated in many cells containing activated tyrosine kinases. This protein, characterized mainly by its avid association with rasGAP, has proved elusive. Anti-phosphotyrosine antibody was used to purify p62. From peptide sequence, molecular cloning revealed a cDNA encoding a novel protein, p62dok, with little homology to others but with a prominent set of tyrosines and nearby sequences suggestive of SH2 binding sites. In cells, v-Abl tyrosine kinase binds and strongly phosphorylates p62dok, which then binds rasGAP. A monoclonal antibody, 2C4, to the rasGAP-associated p62 reacts with p62dok. Thus, p62dok appears to be the long-sought major substrate of many tyrosine kinases.
一种62 kDa的蛋白质在许多含有活化酪氨酸激酶的细胞中高度磷酸化。这种主要以与rasGAP紧密结合为特征的蛋白质一直难以捉摸。抗磷酸酪氨酸抗体被用于纯化p62。通过肽序列分析，分子克隆揭示了一个编码新型蛋白质p62dok的cDNA，它与其他蛋白质几乎没有同源性，但有一组突出的酪氨酸以及附近提示SH2结合位点的序列。在细胞中，v-Abl酪氨酸激酶结合并强烈磷酸化p62dok，然后p62dok结合rasGAP。一种针对与rasGAP相关的p62的单克隆抗体2C4可与p62dok发生反应。因此，p62dok似乎是许多酪氨酸激酶长期以来寻找的主要底物。
