The inositol 5'-phosphatase SHIP binds to immunoreceptor signaling motifs and responds to high affinity IgE receptor aggregation
The inositol 5'-phosphatase SHIP binds to immunoreceptor signaling motifs and responds to high affinity IgE receptor aggregation
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DOI：
10.1074/jbc.271.46.29271
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发表时间：
1996-11-15
影响因子：
4.8
通讯作者：
Kochan, JP
中科院分区：
文献类型：
--
作者：
Osborne, MA;Zenner, G;Kochan, JP
免疫受体如高亲和力IgE受体、Fc ε RI和T细胞受体相关蛋白共有一个共同的基序，即基于免疫受体酪氨酸的激活基序（ITAM）。我们使用酵母三杂交体系统来鉴定磷酸化的Fc γ RI ITAM亚基β和γ的下游效应子。一种新的cDNA被分离出来，它编码一种酪氨酸磷酸化的蛋白质，包含一个Src同源2（SH 2）结构域，肌醇多磷酸酶5-磷酸酶活性，三个NXXY基序，几个富含脯氨酸的区域，被称为SHIP。Fc β RI β或ITAM内保守的酪氨酸或亮氨酸残基的突变消除了SHIP结合，表明SHIP-ITAM相互作用是特异性的。SHIP还在体外结合来自CD 3复合物和T细胞受体ζ链的ITAM。SHIP蛋白具有磷脂酰肌醇-3，4，5-三磷酸5 '-磷酸酶和肌醇-1，3，4，5-四磷酸5'-磷酸酶活性。蛋白酪氨酸激酶Lck使SHIP磷酸化，导致酶活性降低。Fc β RI激活诱导几种酪氨酸磷蛋白与SHIP的结合。SHIP是组成性酪氨酸磷酸化的，与She和Grb 2相关。这些数据表明，SHIP可能作为一个多功能的连接蛋白受体激活。
Immunoreceptors such as the high affinity IgE receptor, Fc epsilon RI, and T-cell receptor associated proteins share a common motif, the immunoreceptor tyrosine-based activation motif (ITAM). We used the yeast tribrid system to identify downstream effecters of the phosphorylated Fc epsilon RI ITAM-containing subunits beta and gamma. One novel cDNA was isolated that encodes a protein that is phosphorylated on tyrosine, contains a Src-homology 2 (SH2) domain, inositolpolyphosphate 5-phosphatase activity, three NXXY motifs, several proline-rich regions, and is called SHIP. Mutation of the conserved tyrosine or leucine residues within the Fc epsilon RI beta or ITAMs eliminates SHIP binding and indicates that the SHIP-ITAM interaction is specific. SHIP also binds to ITAMs from the CD3 complex and T cell receptor zeta chain in vitro. SHIP protein possesses both phosphatidylinositol-3,4,5-trisphosphate 5'-phosphatase and inositol-1,3,4,5-tetrakisphosphate 5'-phosphatase activity. Phosphorylation of SHIP by a protein-tyrosine kinase, Lck, results in a reduction in enzyme activity. Fc epsilon RI activation induces the association of several tyrosine phosphoproteins with SHIP. SHIP is constitutively tyrosine-phosphorylated and associated with She and Grb2. These data suggest that SHIP may serve as a multifunctional linker protein in receptor activation.