Identification of the abl- and rasGAP-associated 62 kDa protein as a docking protein, dok
Identification of the abl- and rasGAP-associated 62 kDa protein as a docking protein, dok
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DOI：
10.1016/s0092-8674(00)81841-3
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发表时间：
1997-01-24
期刊：
影响因子：
64.5
通讯作者：
Baltimore, D
中科院分区：
文献类型：
--
作者：
Yamanashi, Y;Baltimore, D
一个62 kDa的蛋白在许多含有激活的酪氨酸激酶的细胞中高度磷酸化。这种主要以与rasGAP密切结合为特征的蛋白质已被证明是难以捉摸的。用抗磷酸酪氨酸抗体纯化p62。从多肽序列中，分子克隆发现了一个编码新蛋白p62(Dok)的cDNA，与其他蛋白几乎没有同源性，但具有一组显著的酪氨酸和邻近的暗示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p62(Dok)，p62(Dok)然后与rasGAP结合。抗rasGAP相关p62的单抗2C4可与p62(Dok)反应。因此，p62(Dok)似乎是许多酪氨酸激酶长期寻找的主要底物。
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, p62(dok), 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 p62(dok), which then binds rasGAP. A monoclonal antibody, 2C4, to the rasGAP-associated p62 reacts with p62(dok). Thus, p62(dok) appears to be the long-sought major substrate of many tyrosine kinases.