Junctional protein MAGI-3 interacts with receptor tyrosine phosphataseβ (RPTPβ) and tyrosine-phosphorylated proteins
Junctional protein MAGI-3 interacts with receptor tyrosine phosphataseβ (RPTPβ) and tyrosine-phosphorylated proteins
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连接蛋白 MAGI-3 与受体酪氨酸磷酸酶β (RPTPβ) 和酪氨酸磷酸化蛋白相互作用
作者：
K. Adamsky;Katya Arnold;H. Sabanay;E. Peles
受体蛋白酪氨酸磷酸酶β（RPTPβ）介导细胞-细胞和细胞-基质相互作用。通过寻找细胞内的蛋白质相互作用的细胞质区域的磷酸酶使用双杂交的方法，我们确定了几个蛋白质含有PDZ结构域。这些蛋白质之一，MAGI-3，包含一个鸟苷酸激酶样区域，六个PDZ和两个WW结构域。通过免疫共沉淀和pulldown实验证实了RPTPβ和MAGI-3之间的相互作用。免疫荧光和免疫电子显微镜显示，MAGI-3集中在质膜和细胞核的特定位点。在上皮细胞中，MAGI-3与ZO-1和扣带蛋白定位在紧密连接处，而在原代培养的星形胶质细胞中，它被发现在基于E-钙粘蛋白的细胞-细胞接触和粘着斑部位。尽管MAGI-3本身没有在酪氨酸残基上磷酸化，但在用钒酸盐短暂处理细胞后，它与酪氨酸磷酸化蛋白质结合。在胶质母细胞瘤SF 763 T细胞中，MAGI-3与表观分子量为130 kDa的酪氨酸磷酸化蛋白相关，而在Caco 2细胞中，MAGI-3与90 kDa蛋白相关。最后，我们发现p130作为RPTPβ的底物，其去磷酸化需要磷酸酶的C末端序列，该序列介导与MAGI-3的相互作用。这些发现表明MAGI-3作为支架分子的可能作用，该支架分子将受体酪氨酸磷酸酶与其质膜上的底物连接。
Receptor protein tyrosine phosphatase β (RPTPβ) mediates cell-cell and cell-matrix interactions. By searching for intracellular proteins that interact with the cytoplasmic region of this phosphatase using the two-hybrid method, we identified several proteins containing PDZ domains. One of these proteins, MAGI-3, contains a guanylate-kinase-like region, six PDZ and two WW domains. The interaction between RPTPβ and MAGI-3 was confirmed by co-immunoprecipitation and pulldown experiments in transfected cells. Immunofluorescence and immunoelectron microscopy revealed that MAGI-3 is concentrated in specific sites at the plasma membrane and in the nucleus. In epithelial cells, MAGI-3 was localized with ZO-1 and cingulin at tight junctions, whereas in primary cultured astrocytes it was found in E-cadherin-based cell-cell contacts and in focal adhesion sites. Although MAGI-3 itself was not phosphorylated on tyrosine residues, it became associated with tyrosine-phosphorylated proteins following a short treatment of the cells with vanadate. In glioblastoma SF763T cells MAGI-3 was associated with a tyrosine-phosphorylated protein with the apparent molecular weight of 130 kDa, whereas in Caco2 cells it was associated with a 90 kDa protein. Finally, we show that p130 served as a substrate for RPTPβ and that its dephosphorylation required the C-terminal sequence of the phosphatase, which mediated the interaction with MAGI-3. These findings suggest a possible role for MAGI-3 as a scaffolding molecule that links receptor tyrosine phosphatase with its substrates at the plasma membrane.
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DOI：
10.1073/pnas.89.16.7417
发表时间：
1992-08-15
影响因子：
11.1
作者：
KRUEGER, NX;SAITO, H
通讯作者：
SAITO, H
DOI：
10.1073/pnas.93.20.10779
发表时间：
1996-10-01
影响因子：
11.1
作者：
Gottardi, CJ;Arpin, M;Louvard, D
通讯作者：
Louvard, D
影响因子：
3.9
作者：
Dorn, Gerald W., II;Liggett, Stephen B.
通讯作者：
Liggett, Stephen B.
与腱蛋白的相互作用以及对神经组织的两种主要硫酸软骨素蛋白聚糖神经聚糖和磷酸聚糖的细胞粘附的不同影响。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Grumet,M;Milev,P;Sakurai,T;Karthikeyan,L;Bourdon,M;Margolis,RK;Margolis,RU
通讯作者：
Margolis,RU
受体酪氨酸磷酸酶β以蛋白聚糖的形式表达并与细胞外基质蛋白腱蛋白结合。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Barnea,G;Grumet,M;Milev,P;Silvennoinen,O;Levy,JB;Sap,J;Schlessinger,J
通讯作者：
Schlessinger,J