Junctional adhesion molecule-A: functional diversity through molecular promiscuity

Junctional adhesion molecule-A: functional diversity through molecular promiscuity
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连接粘附分子-A:通过分子混杂实现功能多样性

DOI:
10.1007/s00018-017-2729-0
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发表时间:
2018
影响因子:
8
通讯作者:
Ebnet K
Ebnet K
中科院分区:
生物学1区
文献类型:
--
作者:
Steinbacher T;Kummer D;Ebnet K

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免疫球蛋白超家族 (IgSF) 的细胞粘附分子 (CAM) 调节细胞增殖、分化和形态发生等重要过程。这种活性主要是由于它们能够在细胞-细胞接触位点启动细胞内信号级联反应。连接粘附分子-A (JAM-A) 是一种具有短胞质尾部的 IgSF-CAM,不具有催化活性。然而,JAM-A 参与多种生物过程。 JAM-A 的功能多样性很大程度上取决于 C 端 PDZ 结构域结合基序,该基序直接与九种不同的含有 PDZ 结构域的蛋白质相互作用。其 PDZ 结构域基序的分子混杂性使得 JAM-A 能够将蛋白质支架募集到细胞间粘附的特定位点,并在这些位点组装信号复合物。在这里,我们回顾了 JAM-A 的分子特征,包括其二聚化、与支架蛋白的相互作用以及其胞质结构域的磷酸化,并描述了这些特征如何转化为不同的生物活性。
Cell adhesion molecules (CAMs) of the immunoglobulin superfamily (IgSF) regulate important processes such as cell proliferation, differentiation and morphogenesis. This activity is primarily due to their ability to initiate intracellular signaling cascades at cell–cell contact sites. Junctional adhesion molecule-A (JAM-A) is an IgSF-CAM with a short cytoplasmic tail that has no catalytic activity. Nevertheless, JAM-A is involved in a variety of biological processes. The functional diversity of JAM-A resides to a large part in a C-terminal PDZ domain binding motif which directly interacts with nine different PDZ domain-containing proteins. The molecular promiscuity of its PDZ domain motif allows JAM-A to recruit protein scaffolds to specific sites of cell–cell adhesion and to assemble signaling complexes at those sites. Here, we review the molecular characteristics of JAM-A, including its dimerization, its interaction with scaffolding proteins, and the phosphorylation of its cytoplasmic domain, and we describe how these characteristics translate into diverse biological activities.
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