Disease relevance of F11r

• To corroborate these findings, we introduced JAM-A or the structurally related JAM family members JAM-B and JAM-C into Chinese hamster ovary cells, which are poorly permissive for reovirus infection [1].
• Here we report that JAM-A is required for the correct infiltration of polymorphonuclear leukocytes (PMN) into an inflamed peritoneum or in the heart upon ischemia-reperfusion injury [2].
• METHODS AND RESULTS: Here we show that the genetic deletion of JAM-A in apolipoprotein E-deficient (apoE(-/-)) mice significantly reduced neointimal hyperplasia after wire injury of carotid arteries without altering medial area [3].
• Leukocyte recruitment in the cerebrospinal fluid of mice with experimental meningitis is inhibited by an antibody to junctional adhesion molecule (JAM) [4].
• A chimeric adenovirus vector encoding reovirus attachment protein sigma1 targets cells expressing junctional adhesion molecule 1 [5].

High impact information on F11r

• Junctional adhesion molecule proteins localise to intercellular junctions of polarised endothelial and epithelial cells but can also be expressed on circulating leukocytes and platelets [6].
• All these features represent the likely determinants for the role of junctional adhesion molecule proteins in processes as diverse as junction assembly, leukocyte transmigration and platelet activation [6].
• Junctional adhesion molecule (JAM) is a newly cloned member of the immunoglobulin superfamily which is selectively concentrated at tight junctions of endothelial and epithelial cells [4].
• Thus, we identified here a novel, non-redundant role of JAM-A in controlling DC motility, trafficking to lymph nodes, and activation of specific immunity [7].
• Junctional adhesion molecule (JAM) binds to PAR-3: a possible mechanism for the recruitment of PAR-3 to tight junctions [8].

Chemical compound and disease context of F11r

• To determine whether reovirus infection initiated in the absence of JAM-A and sialic acid results in apoptosis, Chinese hamster ovary (CHO) cells engineered to express Fc receptors were infected with reovirus using antibodies directed against viral outer-capsid proteins [9].

Biological context of F11r

• Furthermore, in vitro binding and transfection experiments showed that junctional adhesion molecule, another TJ adhesion molecule, also bound to the PDZ9 domain of MUPP1 [10].
• The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM) [11].
• X-ray structure of junctional adhesion molecule: structural basis for homophilic adhesion via a novel dimerization motif [12].
• Thus, we show for the first time that JAM-A is up-regulated in hepatic venules and serves as an endothelial receptor of neutrophil transmigration, but it does not mediate leukocyte rolling, adhesion, or platelet-endothelial cell interactions [13].
• Thus, by regulating cytoskeletal and adhesive structures, JAM-A expression prevents cell motility, probably in a PSD95-Dlg-ZO1-dependent manner [14].

Anatomical context of F11r

• These findings suggested that MUPP1 is concentrated at TJs in epithelial cells through its binding to claudin and junctional adhesion molecule and that it may function as a multivalent scaffold protein that recruits various proteins to TJs [10].
• Treatment with the gap junction blocker 18beta-glycyrrhetinic acid did not affect expression of MAGI-1 and JAM-1 in Cx32 transfectants [15].
• We report here the identification of a novel protein (junctional adhesion molecule [JAM]) that is selectively concentrated at intercellular junctions of endothelial and epithelial cells of different origins [16].
• Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration [16].
• In vitro, in the absence of JAM-A, PMN adhered more efficiently to endothelial cells and basement membrane proteins, and their polarized movement was strongly reduced [2].

Associations of F11r with chemical compounds

• The I/R-induced increase in the activity of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and sinusoidal perfusion failure was not reduced in JAM-A-/- mice, while the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL)-positive hepatocytes was significantly higher [13].
• Junctional adhesion molecule (JAM)-C is expressed at different levels on endothelial cells of lymphoid organs and peripheral tissues and has been proposed to regulate neutrophil migration by its interaction with the leukocyte integrin Mac-1 [17].
• Junctional adhesion molecule-A (JAM-A) is a cell-surface glycoprotein that localizes to intercellular junctions and associates with intracellular proteins via PSD95-Dlg-ZO1-binding residues [14].
• A mechanism underlying reduced recruitment was implied by findings that the luminal expression of the arrest chemokine RANTES in injured arteries and its endothelial deposition by activated platelets in vitro were diminished by JAM-A deficiency [3].
• These data provide strong evidence that Ad5-T3Dsigma1 can be redirected to cells expressing JAM1 and sialic acid for application as a vaccine vector [5].

Physical interactions of F11r

• PAR-3 is a cell polarity protein that localizes at tight junctions (TJs) by direct binding to an immunoglobulin (Ig)-like cell-cell adhesion molecule JAM-1 in mammalian epithelial cells [18].

Regulatory relationships of F11r

• Thus, JAM-A expression may regulate effectors of motility that are also downstream of the PKCzeta/GSK-3beta axis [14].
• OBJECTIVE: We have previously shown that JAM-A regulates fibroblast growth factor-2 (FGF-2)-induced endothelial cell morphology, proliferation, and migration [19].

Other interactions of F11r

• Another Ig-like cell-cell adhesion molecule nectin plays a role in the localization of JAM-1 at TJs in epithelial cells [18].
• Immunofluorescence confocal analysis of staged embryos and synchronized cell clusters revealed JAM-1 recruitment to cell contact sites occurred predominantly during the first hour after division to the eight-cell stage, earlier than any other TJ protein analysed to date in this model and before E-cadherin adhesion and cell polarization [20].
• We identified a novel junctional adhesion molecule, named JAM-2, by a selective RNA display method, which allowed identification of transcripts encoding immunoglobulin superfamily molecules regulated during coculture of endothelial cells with tumor cells [21].
• In contrast to JAM-1, however, the 1G8 antigen does not associate with the PDZ domain proteins ZO-1, AF-6, or ASIP/PAR-3, despite the presence of a PDZ-binding motif [22].
• We investigated the role of beta2-integrins and their major counter-receptors (intercellular adhesion molecule-1 (ICAM-1), receptor for advanced glycation endproducts (RAGE), junctional adhesion molecule (JAM)-C) in obstructive nephropathy in neonatal mice [23].
• Using a leukocyte transfer method and mice deficient in endothelial-cell JAM-A, evidence was obtained for the involvement of endothelial-cell JAM-A in leukocyte transmigration mediated by IL-1beta [24].

Analytical, diagnostic and therapeutic context of F11r

• Adoptive transfer experiments showed that JAM-A-deficient DCs elicited increased CHS in Jam-A(+/+) mice, further supporting the concept of a DC-specific effect [7].
• We show that JAM-A is up-regulated in hepatic venular endothelium during reperfusion [13].
• Northern blot analysis indicated that JAM-1 mRNA is expressed as multiple species, the predominant transcript being approximately 4.0 kb in size [25].
• The study reported here obtained in-vivo confirmation of this conclusion by investigating F11R/JAM-A protein and mRNA in patients with aortic and peripheral vascular disease and in an animal model of atherosclerosis [26].
• Epidemiological studies, clinical intervention trials (including the trial with selenium-enriched yeast by Clark et al. JAMA 276, 1957, 1996) and assays in laboratory animals provide evidence for a protective role of selenium against the development of several cancers, including lung cancer [27].

References