Activation of Protein-tyrosine Phosphatase SH-PTP2 by a Tyrosine-based Activation Motif of a Novel Brain Molecule*
Activation of Protein-tyrosine Phosphatase SH-PTP2 by a Tyrosine-based Activation Motif of a Novel Brain Molecule*
复制标题
通过新型脑分子的基于酪氨酸的激活基序激活蛋白酪氨酸磷酸酶 SH-PTP2*
DOI：
10.1074/jbc.271.41.25569
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
S. Sano
中科院分区：
文献类型：
--
作者：
H. Ohnishi;M. Kubota;A. Ohtake;Kazuki Sato;S. Sano
BIT（一种具有基于酪氨酸的激活基序的雨免疫球蛋白样分子）是脑特异性膜蛋白，其具有两个细胞质TAM（基于酪氨酸的激活基序）。使用远Western印迹技术，我们检测到协会的70 kDa的蛋白与酪氨酸磷酸化的TAM的位。从小鼠脑cDNA文库中筛选了λ gt 11的这种关联，并分离出两个编码酪氨酸磷酸酶SH-PTP 2的阳性克隆。SH-PTP 2具有两个SH 2结构域，并且被认为在受体酪氨酸激酶信号传导中起正介体的作用。SH-PTP 2和BIT从磷酸化的大鼠脑裂解物中共免疫沉淀，BIT是该裂解物中与SH-PTP 2相关的主要酪氨酸磷酸化蛋白。在用BIT cDNA转染的Jurkat T细胞中也观察到这种相互作用，这取决于BIT的酪氨酸磷酸化。BIT-TAM对应的双磷酸酪氨酸肽在体外刺激SH-PTP 2活性33-35倍，表明SH-PTP 2的两个SH 2结构域同时与BIT-TAM的两个磷酸酪氨酸相互作用。我们的研究结果表明，BIT的酪氨酸磷酸化的结果在刺激的信号转导通路促进SH-PTP 2和BIT可能是一个主要的受体分子在大脑中位于上游的SH-PTP 2。
BIT (a rain mmunoglobulin-like molecule with yrosine-based activation motifs) is a brain-specific membrane protein which has two cytoplasmic TAMs (yrosine-based ctivation otifs). Using the Far Western blotting technique, we detected association of a 70-kDa protein with the tyrosine-phosphorylated TAMs of BIT. A mouse brain cDNA library in λgt11 was screened for this association, and two positive clones encoding tyrosine phosphatase SH-PTP2 were isolated. SH-PTP2 has two SH2 domains and is believed to function as a positive mediator in receptor tyrosine kinase signaling. SH-PTP2 and BIT were coimmunoprecipitated from phosphorylated rat brain lysate, and BIT was a major tyrosine-phosphorylated protein associated with SH-PTP2 in this lysate. This interaction was also observed in Jurkat T cells transfected with BIT cDNA depending on tyrosine phosphorylation of BIT. Bisphosphotyrosyl peptides corresponding to BIT-TAMs stimulated SH-PTP2 activity 33-35-fold in vitro, indicating that two SH2 domains of SH-PTP2 simultaneously interact with two phosphotyrosines of BIT-TAM. Our findings suggest that the tyrosine phosphorylation of BIT results in stimulation of the signal transduction pathway promoted by SH-PTP2 and that BIT is probably a major receptor molecule in the brain located just upstream of SH-PTP2.
登录
查看更多内容
胰岛素受体底物 1 与含有 SH2 的磷酸酪氨酸磷酸酶 Syp 结合。
DOI：
--
发表时间：
1993
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kuhné,MR;Pawson,T;Lienhard,GE;Feng,GS
通讯作者：
Feng,GS
DOI：
10.1016/s0021-9258(17)36874-6
发表时间：
1994-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
S. Sugimoto;T. Wandless;S. Shoelson;B. Neel;C. Walsh
通讯作者：
S. Sugimoto;T. Wandless;S. Shoelson;B. Neel;C. Walsh
DOI：
10.1073/pnas.89.23.11239
发表时间：
1992-12-01
影响因子：
11.1
作者：
FREEMAN, RM;PLUTZKY, J;NEEL, BG
通讯作者：
NEEL, BG
DOI：
10.1073/pnas.91.15.7335
发表时间：
1994-07-19
影响因子：
11.1
作者：
BENNETT, AM;TANG, TL;NEEL, BG
通讯作者：
NEEL, BG
影响因子：
2.9
作者：
OTTINGER, EA;SHEKELS, LL;BARANY, G
通讯作者：
BARANY, G