The 145-kDa protein induced to associate with Shc by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase

The 145-kDa protein induced to associate with Shc by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase
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DOI:
10.1073/pnas.93.4.1689
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发表时间:
1996-02-20
影响因子:
11.1
通讯作者:
Krystal, G
Krystal, G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Damen, JE;Liu, L;Krystal, G

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已经从鼠造血细胞系B6 SUtA中纯化了一种145-kDa酪氨酸磷酸化蛋白质,该蛋白质响应于多种细胞因子而与She结合(1)。使用氨基酸序列数据从B6 SUtA(1)文库中克隆编码该蛋白的cDNA。预测的氨基酸序列编码一个独特的蛋白质,包含一个N-末端src同源2域,两个共识序列,磷酸酪氨酸结合域的目标,脯氨酸丰富的区域,和两个图案之间高度保守的肌醇多磷酸5-磷酸酶。用抗血清免疫沉淀该蛋白质的细胞裂解物表现出磷脂酰肌醇3,4,5-三磷酸和肌醇1,3,4,5-四磷酸多磷酸5-磷酸酶活性。这种新的信号转导中间体可能起到调节Ras和肌醇信号通路的作用。基于其性质,我们建议将145-kDa蛋白质称为SHIP,即含SH 2的肌醇磷酸酶。
A 145-kDa tyrosine-phosphorylated protein that becomes associated with She in response to multiple cytokines has been purified from the murine hemopoietic cell line B6SUtA(1). Amino acid sequence data were used to clone the cDNA encoding this protein from a B6SUtA(1) library. The predicted amino acid sequence encodes a unique protein containing an N-terminal src homology 2 domain, two consensus sequences that are targets for phosphotyrosine binding domains, a proline-rich region, and two motifs highly conserved among inositol polyphosphate 5-phosphatases. Cell lysates immunoprecipitated with antiserum to this protein exhibited both phosphatidylinositol 3,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate polyphosphate 5-phosphatase activity. This novel signal transduction intermediate may serve to modulate both Ras and inositol signaling pathways. Based on its properties, we suggest the 145-kDa protein be called SHIP for SH2-containing inositol phosphatase.