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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2009-6-22
pubmed:abstractText
Junctional adhesion molecule A (JAM-A) is a tight junction-associated, PDZ binding domain containing transmembrane protein that forms cis-homodimers in endothelial and epithelial cells. In vivo, the function of JAM-A in colonic mucosa has been examined using JAM-A knockout mice, which have increased intestinal permeability, inflammation and cellular proliferation compared to wild-type controls. In vitro studies have revealed that downregulation of JAM-A leads to altered cell migration secondary to diminished levels of beta1 integrin on the cell surface. Similar findings have been observed after transfection of epithelial cells with mutant JAM-A, which is defective in dimerization or lacks the PDZ binding domain. The dominant-negative effects of these mutant JAM-A proteins are most likely secondary to the inability of mutant JAM-A to form signaling complexes, the lack of which results in decreases in active or GTP-bound Rap1. This review highlights findings that support a hypothetical model for JAM-A mediated outside-in signaling. In this model, JAM-A dimerization is required for close cytoplasmic apposition of complexes containing specific PDZ domain-containing scaffold proteins that activate signaling molecules to serve as effectors for the regulation of cellular functions. The possibility of interactions of JAM-A cis-dimers between cells in trans is also discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1749-6632
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
1165
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10-8
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Mechanisms of outside-in signaling at the tight junction by junctional adhesion molecule A.
pubmed:affiliation
Epithelial Pathobiology Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
pubmed:publicationType
Journal Article, Review