Zondag G C, Koningstein G M, Jiang Y P, Sap J, Moolenaar W H, Gebbink M F
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam.
J Biol Chem. 1995 Jun 16;270(24):14247-50. doi: 10.1074/jbc.270.24.14247.
The receptor-like protein tyrosine phosphatases (RPTP) mu and RPTP kappa have a modular ectodomain consisting of four fibronectin type III-like repeats, a single Ig-like domain, and a newly identified N-terminal MAM domain. The function of the latter module, which comprises about 160 amino acids and is found in diverse transmembrane proteins, is not known. We previously reported that both RPTP mu and RPTP kappa can mediate homophilic cell interactions when expressed in insect cells. Here we show that despite their striking structural similarity, RPTP mu and RPTP kappa fail to interact in a heterophilic manner. To examine the role of the MAM domain in homophilic binding, we expressed a mutant RPTP mu lacking the MAM domain in insect Sf9 cells. Truncated RPTP mu is properly expressed at the cell surface but fails to promote cell-cell adhesion. Homophilic cell adhesion is fully restored in a chimeric RPTP mu molecule containing the MAM domain of RPTP kappa. However, this chimeric RPTP mu does not interact with either RPTP mu or RPTP kappa. These results indicate that the MAM domain of RPTP mu and RPTP kappa is essential for homophilic cell-cell interaction and helps determine the specificity of these interactions.
类受体蛋白酪氨酸磷酸酶（RPTP）μ和RPTPκ具有模块化的胞外结构域，该结构域由四个纤连蛋白III型样重复序列、一个单一的免疫球蛋白样结构域和一个新鉴定的N端MAM结构域组成。后一个模块由约160个氨基酸组成，存在于多种跨膜蛋白中，其功能尚不清楚。我们之前报道过，RPTPμ和RPTPκ在昆虫细胞中表达时都能介导同种型细胞间相互作用。在此我们表明，尽管RPTPμ和RPTPκ在结构上有显著相似性，但它们不能以异嗜性方式相互作用。为了研究MAM结构域在同种型结合中的作用，我们在昆虫Sf9细胞中表达了缺失MAM结构域的突变型RPTPμ。截短的RPTPμ在细胞表面正确表达，但不能促进细胞间黏附。在含有RPTPκ的MAM结构域的嵌合RPTPμ分子中，同种型细胞黏附完全恢复。然而，这种嵌合RPTPμ既不与RPTPμ相互作用，也不与RPTPκ相互作用。这些结果表明，RPTPμ和RPTPκ的MAM结构域对于同种型细胞间相互作用至关重要，并有助于确定这些相互作用的特异性。
