p62(dok): A constitutively tyrosine-phosphorylated, GAP-associated protein in chronic myelogenous leukemia progenitor cells

p62(dok): A constitutively tyrosine-phosphorylated, GAP-associated protein in chronic myelogenous leukemia progenitor cells
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DOI:
10.1016/s0092-8674(00)81840-1
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发表时间:
1997-01-24
期刊:
影响因子:
64.5
通讯作者:
Clarkson, B
Clarkson, B
中科院分区:
生物学1区
文献类型:
--
作者:
Carpino, N;Wisniewski, D;Clarkson, B

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慢性粒细胞白血病 (CML) 的特征是存在嵌合 p210(bcr-abl) 蛋白,该蛋白相对于正常的 c-abl 酪氨酸激酶具有升高的蛋白酪氨酸激酶活性。从慢性期 CML 患者中分离的造血祖细胞含有组成型酪氨酸磷酸化蛋白,通过 SDS-PAGE 检测,该蛋白以 62 kDa 迁移,并与 p120 ras GTP 酶激活蛋白 (GAP) 结合。我们从表达 p210(bcr-abl) 的造血细胞系中纯化了 p62(dok)。 p62(dok) 是一种具有信号分子特征的新型蛋白质。 p62(dok) 与 GAP 的关联与其酪氨酸磷酸化相关。 p62(dok) 在 c-Kit 受体激活后迅速被酪氨酸磷酸化,这表明它是受体酪氨酸激酶下游信号转导途径的一个组成部分。
Characteristic of chronic myelogenous leukemia (CML) is the presence of the chimeric p210(bcr-abl) protein possessing elevated protein tyrosine kinase activity relative to normal c-abl tyrosine kinase. Hematopoietic progenitors isolated from CML patients in the chronic phase contain a constitutively tyrosine-phosphorylated protein that migrates at 62 kDa by SDS-PAGE and associates with the p120 ras GTPase-activating protein (GAP). We have purified p62(dok) from a hematopoietic cell line expressing p210(bcr-abl). p62(dok) is a novel protein with features of a signaling molecule. Association of p62(dok) with GAP correlates with its tyrosine phosphorylation. p62(dok) is rapidly tyrosine-phosphorylated upon activation of the c-Kit receptor, implicating it as a component of a signal transduction pathway downstream of receptor tyrosine kinases.