Structural determinants of Junctional Adhesion Molecule A (JAM-A) function and mechanisms of intracellular signaling

EA Severson, CA Parkos - Current opinion in cell biology, 2009 - Elsevier
Current opinion in cell biology, 2009Elsevier
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 …
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 β1 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.
Elsevier