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lüll Structural determinants of Junctional Adhesion Molecule A (JAM-A) function and mechanisms of intracellular signaling Severson EA; Parkos CACurr Opin Cell Biol 2009[Oct]; 21 (5): 701-7Junctional 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.|*Signal Transduction[MESH]|Animals[MESH]|Cell Adhesion Molecules/*chemistry/*metabolism[MESH]|Cell Membrane Permeability[MESH]|Cell Movement[MESH]|Humans[MESH]|Intracellular Space/chemistry/*metabolism[MESH]|Junctional Adhesion Molecules[MESH] |