Molecular cloning and characterization of p56dok-2 defines a new family of RasGAP-binding proteins
Molecular cloning and characterization of p56dok-2 defines a new family of RasGAP-binding proteins
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DOI：
10.1074/jbc.273.9.4827
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发表时间：
1998-02-27
影响因子：
4.8
通讯作者：
Resh, MD
中科院分区：
文献类型：
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作者：
Di Cristofano, A;Carpino, N;Resh, MD
慢性粒细胞白血病（CML）是一种以p210（bcr-abl）存在为特征的疾病，p210是一种具有酪氨酸激酶活性的嵌合蛋白。p210（bcr-abl）的底物可能参与CML的发病机制。本文描述了从p210（bcr-abl）表达细胞中纯化、cDNA克隆和鉴定56-kDa酪氨酸磷酸化蛋白p56（dok-2）（Dok-2）。人dok-2 cDNA编码412个氨基酸的蛋白，具有预测的N-末端pleckstrin同源结构域以及信号分子的几个其它特征，包括13个潜在的酪氨酸磷酸化位点，六个PXXP基序，以及与p120（RasGAP）结合的能力。Dok-2被证明是35%相同的p62（dok-1），最近确定的RasGAP结合蛋白从CML细胞，和表达的序列标签数据库的分析显示，存在至少四个额外的蛋白质含有Dok同源序列基序。Dok mRNA主要在造血来源的组织中表达。这些发现有力地表明，Dok相关蛋白家族的存在，结合RasGAP，并可能介导p210（bcr-abl）在CML中的作用。
Chronic myelogenous leukemia (CML) is a disease characterized by the presence of p210(bcr-abl), a chimeric protein with tyrosine kinase activity. Substrates for p210(bcr-abl) are likely to be involved in the pathogenesis of CML. Here we describe the purification, cDNA cloning, and characterization of a 56-kDa tyrosine phosphorylated protein, p56(dok-2) (Dok-2), from p210(bcr-abl) ex pressing cells, The human dok-2 cDNA encodes a 412-amino acid protein with a predicted N-terminal pleckstrin homology domain as well as several other features of a signaling molecule, including 13 potential tyrosine phosphorylation sites, six PXXP motifs, and the ability to bind to p120(RasGAP). Dok-2 was shown to be 35% identical to p62(dok-1), a recently identified RasGAP binding protein from CML cells, and analysis of the expressed sequence tag data base revealed the presence of at least four additional proteins containing a Dok homology sequence motif. Dok mRNAs were primarily expressed in tissues of hematopoietic origin. These findings strongly suggest that a family of Dok-related proteins exists that bind to RasGAP and may mediate the effects of p210(bcr-abl) in CML.