Severson Eric A, Parkos Charles A
Department of Pathology and Laboratory Medicine, Emory University, 615 Michael Street, Atlanta, GA 30322, USA.
Curr Opin Cell Biol. 2009 Oct;21(5):701-7. doi: 10.1016/j.ceb.2009.06.005. Epub 2009 Jul 14.
Junctional Adhesion Molecule A (JAM-A) is a multifunctional cell surface protein that has multiple evolutionarily conserved structural features. There is now conclusive evidence that discrete structural elements on JAM-A mediate intracellular signaling events that alter cell migration and paracellular permeability. Specifically, self-dimerization between extracellular Ig-like loops and close apposition of PDZ-dependent, JAM-A-associated intracellular scaffold proteins such as Afadin and guanine-nucleotide exchange factors mediate activation of Rap1 and modulation of epithelial cell migration by effects on beta1 integrin. While the same JAM-A structural features also modulate migration of other cell types and paracellular permeability in epithelia/endothelia, additional signaling proteins/mechanisms are probably involved. Recent insights into JAM-A outside-in signaling events that regulate these cellular functions are discussed.
连接粘附分子A（JAM-A）是一种多功能细胞表面蛋白，具有多种进化保守的结构特征。现在有确凿的证据表明，JAM-A上离散的结构元件介导细胞内信号传导事件，这些事件会改变细胞迁移和细胞旁通透性。具体而言，细胞外免疫球蛋白样环之间的自二聚化以及依赖PDZ的JAM-A相关细胞内支架蛋白（如Afadin）和鸟嘌呤核苷酸交换因子的紧密并置，通过对β1整合素的作用介导Rap1的激活和上皮细胞迁移的调节。虽然相同的JAM-A结构特征也调节其他细胞类型的迁移以及上皮/内皮细胞的细胞旁通透性，但可能涉及其他信号蛋白/机制。本文讨论了对调节这些细胞功能的JAM-A外向内信号传导事件的最新见解。
