Disease relevance of F11R

• A pathophysiological role for the F11R was revealed by demonstrating the presence of F11R-antibodies in patients with thrombocytopenia [1].
• Agents that block the F11R-mediated adhesion of platelets to EC may be of therapeutic value in controlling thrombosis and preventing heart attacks and stroke [2].
• 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 [3].
• To further examine critical sites of F11R, we utilized the baculovirus system to generate the F11R recombinant protein with the sequence of the extracellular domain, in two types of insect cells, Sf9 and H5 [4].
• Neutrophil migration across tight junctions is mediated by adhesive interactions between epithelial coxsackie and adenovirus receptor and a junctional adhesion molecule-like protein on neutrophils [5].

Psychiatry related information on F11R

• JAMA patient page. Attention-deficit/hyperactivity disorder [6].
• JAMA patient page. Mental retardation [7].
• [1991: JAMA 266: 1793-1800] have recently reported a highly significant association between Tourette's syndrome (TS) and a restriction fragment length polymorphism (RFLP) of the dopamine D2 receptor gene (DRD2) locus [8].
• After treatment, we defined response to therapy as a 40% reduction from baseline on Panic Disorder Severity Scale (PDSS) score as described by [Barlow, D.H., Gorman, J.M., Shear, M.K., Woods, S.W., 2000. Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: A randomized controlled trial. JAMA. 283, 2529-2536] [9].
• JAMA patient page. Smoking cessation [10].

High impact information on F11R

• JAMA patient page. Colon cancer screening [11].
• JAMA patient page. Obesity [12].
• JAMA patient page. Hepatitis C [13].
• JAMA patient page. Pressure ulcers [14].
• JAMA patient page. Mastitis [15].

Chemical compound and disease context of F11R

• This may explain some of the large regional odds ratio variation for dipyrone-related agranulocytosis in the International Agranulocytosis and Aplastic Anemia Study (JAMA 1986; 256: 1749-1757 [16].
• We measured the endogenous levels of KYNA and activities of KYNA synthesizing enzymes kynurenine aminotransferase I (KAT I) and kynurenine aminotransferase II (KAT II) in the frontal and temporal cortex of elderly Down syndrome (DS) patients (aged 46-69 years) [17].
• The current study analysed kynurenine aminotransferase I (KAT I) activity and kynurenic acid (KYNA) concentrations in human senile cataractous lenses and in experimentally induced cataracts in diabetic rats treated with streptozotocin (STZ) [18].
• Letter to the editor re: JAMA article on L-arginine therapy in acute myocardial infarction [19].
• The ASTEROID trial (JAMA 2006; 295:1556-1565) showed that very intensive statin therapy with rosuvastatin 40 mg once daily results in highly significant regression of coronary atherosclerosis as assessed by serial intravascular ultrasonography (IVUS) [20].

Biological context of F11R

• Adhesion of platelets through the F11R resulted in events characteristic of the action of cell adhesion molecules (CAMs) [1].
• The F11R is a 32-/35-kd protein duplex that serves as the binding site through which a stimulatory monoclonal antibody causes platelet aggregation and granule secretion [1].
• A physiological role for the F11R protein was demonstrated by its phosphorylation after the stimulation of platelets by thrombin and collagen [1].
• Modeling of the 3D structure of the extracellular domain of the human platelet F11R suggests that these two regions form an active site within the conformation of this CAM [21].
• This is evidenced by the inhibition of platelet adhesion to endothelial cells by recombinant soluble form of the F11R, and by two F11R peptides with amino acid sequences of the N-terminal region, and in the 1(st) Ig fold of the F11R, respectively [2].

Anatomical context of F11R

• The role of F11R/JAM in the interaction of platelets with endothelial cells was investigated in the current studies [2].
• Furthermore, platelets adhere to cytokine- (TNF-alpha, INF-gamma) stimulated human umbilical vein endothelial cells (HUVEC), and approximately 40-60% of the adhesive force is exerted by homophilic interactions between the F11R of platelets and EC [2].
• This study suggests a role for F11R in the adhesion of platelets to cytokine-inflamed endothelial cells and thus in thrombosis and atherosclerosis induced in non-denuded blood vessels by inflammatory processes [2].
• We demonstrate that platelet secretion and aggregation through the F11R involves actin filament assembly that is dependent on phosphoinositide-3 kinase activation, and inhibitable by wortmannin [22].
• On the other hand, F11R-mediated events resulting from the binding of platelets to an immobilized surface of M.Ab.F11 lead to platelet adhesion and spreading through the development of filopodia and lammelipodia [22].

Associations of F11R with chemical compounds

• Lastly, knockdown of Rap1b resulted in diminished beta1 integrin expression and altered cell morphology analogous to that observed with knockdown of JAM1 [23].
• DD enabled us to detect seven overexpressed mRNAs during treatment, four of which corresponded to identified genes: aldehyde dehydrogenase 1, nuclear transcription factor Nrfl, junctional adhesion molecule, and amino-ketobutyrate ligase [24].
• Assessment of the phosphorylation state in the recombinant F11R protein revealed phosphorylation of serine, threonine and tyrosine amino acid residues within the external domain [4].
• We report here that junctional adhesion molecule (JAM) interacts with calcium/calmodulin-dependent serine protein kinase (CASK), a protein related to membrane-associated guanylate kinases [25].
• PARTICIPANTS--All first authors of scientific articles published in JAMA and The New England Journal of Medicine during a 6-month period [26].

Physical interactions of F11R

• We have identified the PDZ domain protein AF-6 as an intracellular binding partner of the junctional adhesion molecule (JAM), an integral membrane protein located at cell contacts [27].
• The fully human monoclonal IgM antibody PAM-1 was isolated from a patient with stomach carcinoma and binds to a new variant of cysteine-rich fibroblast growth factor receptor 1 (CFR-1) [28].

Co-localisations of F11R

• Junctional adhesion molecule (JAM) is an integral membrane protein that has been reported to colocalize with the tight junction molecules occludin, ZO-1, and cingulin [29].

Regulatory relationships of F11R

• Junctional adhesion molecule 1 regulates epithelial cell morphology through effects on beta1 integrins and Rap1 activity [23].
• OBJECTIVE: Recently, we have shown that blocking of junctional adhesion molecule-1/A (JAM-1/A) inhibits basic fibroblast growth factor (bFGF)-induced angiogenesis [30].
• Immunoelectron microscopy demonstrates accumulation of PAM and ACTH in tubular structures at the trans side of the Golgi in AtT-20 cells expressing PAM-1 but not in AtT-20 cells expressing PAM-1/K919R [31].
• Here, we show that, when ectopically expressed in human umbilical vein endothelial cells (HUVECs), JAM-A induced enhanced cell migration on vitronectin, but had no effect on fibronectin [32].
• Bacterial lipopolysaccharide and a monocyte chemotactic protein preparation respectively suppressed and upregulated PAM-1 expression in monocyte-derived macrophages [33].

Other interactions of F11R

• Interestingly, knockdown of JAM1 also produced dramatic changes in cell morphology, and a similar effect was observed with expression of a JAM1 mutant lacking the putative homodimer interface [23].
• We typed 22 variants in the F11R/USF1 region (1 per 3 kb), including those previously implicated in FCHL-susceptibility (or proxies thereof) in 3,726 samples preferentially enriched for 1q linkage [34].
• The tight junction membrane domain contains at least three distinct proteins, named occludin, claudin and junctional adhesion molecule [35].
• Claudin-5, occludin, and JAM-1 did not change significantly as a function of gestational age [36].
• Essential role of junctional adhesion molecule-1 in basic fibroblast growth factor-induced endothelial cell migration [30].

Analytical, diagnostic and therapeutic context of F11R

• This study demonstrates that the human platelet F11 receptor (F11R) functions as an adhesion molecule, and this finding is confirmed by the structure of the protein as revealed by molecular cloning [1].
• Immunoprecipitation analysis suggests that bFGF signaling dissociates the JAM-1/ alphavbeta3 complex, allowing for signaling through JAM-1 and alphavbeta3 [37].
• Epitope mapping by phage display revealed that both inhibitory antibodies bind to a region of JAM1 located within the N-terminal Ig-like loop (residues 111-123) [38].
• Immunocytochemistry and semiquantitative confocal microscopy for JAM-A and beta-catenin was performed on snap-frozen sections from MS cases (n = 11) and controls (n = 6) [39].
• JAMA patient page. Palliative care [40].

References