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MAM(金属蛋白酶/载脂蛋白A5/蛋白酪氨酸磷酸酶μ)结构域是一个促进受体样蛋白酪氨酸磷酸酶μ侧向二聚化的同源结合位点。

The MAM (meprin/A5-protein/PTPmu) domain is a homophilic binding site promoting the lateral dimerization of receptor-like protein-tyrosine phosphatase mu.

作者信息

Cismasiu Valeriu B, Denes Stefan A, Reiländer Helmut, Michel Hartmut, Szedlacsek Stefan E

机构信息

Department of Enzymology, Institute of Biochemistry, Spl. Independentei 296, Bucharest 060031, Romania.

出版信息

J Biol Chem. 2004 Jun 25;279(26):26922-31. doi: 10.1074/jbc.M313115200. Epub 2004 Apr 14.

Abstract

The MAM (meprin/A5-protein/PTPmu) domain is present in numerous proteins with diverse functions. PTPmu belongs to the MAM-containing subclass of protein-tyrosine phosphatases (PTP) able to promote cell-to-cell adhesion. Here we provide experimental evidence that the MAM domain is a homophilic binding site of PTPmu. We demonstrate that the MAM domain forms oligomers in solution and binds to the PTPmu ectodomain at the cell surface. The presence of two disulfide bridges in the MAM molecule was evidenced and their integrity was found to be essential for MAM homophilic interaction. Our data also indicate that PTPmu ectodomain forms oligomers and mediates the cellular adhesion, even in the absence of MAM domain homophilic binding. Reciprocally, MAM is able to interact homophilically in the absence of ectodomain trans binding. The MAM domain therefore contains independent cis and trans interaction sites and we predict that its main role is to promote lateral dimerization of PTPmu at the cell surface. This finding contributes to the understanding of the signal transduction mechanism in MAM-containing PTPs.

摘要

MAM(金属蛋白酶/载脂蛋白A5/蛋白酪氨酸磷酸酶μ)结构域存在于许多具有不同功能的蛋白质中。蛋白酪氨酸磷酸酶μ属于含MAM结构域的蛋白酪氨酸磷酸酶(PTP)亚类,能够促进细胞间黏附。在此,我们提供实验证据表明MAM结构域是蛋白酪氨酸磷酸酶μ的同源结合位点。我们证明MAM结构域在溶液中形成寡聚体,并在细胞表面与蛋白酪氨酸磷酸酶μ的胞外结构域结合。已证实MAM分子中存在两个二硫键,且发现它们的完整性对于MAM同源相互作用至关重要。我们的数据还表明,即使在没有MAM结构域同源结合的情况下,蛋白酪氨酸磷酸酶μ的胞外结构域也能形成寡聚体并介导细胞黏附。相反,在没有胞外结构域反式结合的情况下,MAM能够进行同源相互作用。因此,MAM结构域包含独立的顺式和反式相互作用位点,我们预测其主要作用是促进蛋白酪氨酸磷酸酶μ在细胞表面的侧向二聚化。这一发现有助于理解含MAM结构域的蛋白酪氨酸磷酸酶中的信号转导机制。

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