Disease relevance of Gpr172b

• Here we show that the KSHV GPCR enhances the expression of VEGF by stimulating the activity of the transcription factor hypoxia-inducible factor (HIF)-1alpha, which activates transcription from a hypoxia response element within the 5'-flanking region of the VEGF promoter [1].
• The expression of PAR-2 in synovial tissues from rheumatoid arthritis (RA) and osteoarthritis (OA) patients was compared [2].
• Our data thus provide ultimate evidence for role of PAR2 in colonic hypersensitivity, and suggest involvement of the bradykinin-B2 pathway [3].

High impact information on Gpr172b

• METHODS: Using a monoclonal antibody to human PAR-2, expression in RA synovium and cultured synovial fibroblasts was characterized [4].
• OBJECTIVE: Serine proteinases activate the G protein-coupled receptor, proteinase-activated receptor 2 (PAR-2), via cleavage and exposure of a tethered ligand [4].
• RESULTS: In AIA, arthritis was significantly decreased in PAR-2-deficient mice and was associated with decreased levels of anti-mBSA IgG antibodies and lymph node cell proliferation [2].
• GPCR-dependent ROS formation is absent in lipopolysaccharide (LPS)-primed P-Rex1(-/-) neutrophils, but less affected in unprimed or TNFalpha-primed cells [5].
• Here we show that a serine protease acting via protease-activated receptor-2 (PAR-2) stimulates the development of DC from bone marrow progenitor cells cultured in granulocyte-macrophage colony-stimulating factor and IL-4 [6].

Chemical compound and disease context of Gpr172b

• Intracolonic (i.col.) administration of the PAR2-activating peptide (PAR2AP) SLIGRL-NH(2) slowly develops visceral hypersensitivity to i.col. capsaicin in ddY mice [3].
• The PAR2-triggered visceral hypersensitivity was abolished by a bradykinin B2 receptor antagonist, HOE-140 [3].

Biological context of Gpr172b

• We hypothesized here that PAR-2 plays a central role in epidermal permeability barrier homeostasis by mediating signaling from serine proteases (SP) in the stratum corneum (SC) [7].
• These data show for the first time the role of G protein receptor phosphorylation and internalization per se in the regulatory function of an endocrine system controlled by a GPCR [8].
• Thirdly, topical applications of PAR-2 agonist peptide, SLIGRL, delay permeability barrier recovery and inhibit LB secretion, while, conversely, PAR-2 knockout mice display accelerated barrier recovery kinetics and enhanced LB secretion, paralleled by increased LR formation and caveolin-1 expression [7].
• Vasoconstriction elicited by angiotensin II (Ang II) or phenylephrine (PE), G-protein-coupled receptor (GPCR) agonists, but not that elicited by arachidonic acid or KCl, was greater in eNOS KO mice [9].
• Ca(2+) imaging in WT acinar cells and beta-galactosidase staining in PAR-2KO mice, in which the beta-galactosidase gene (LacZ) was incorporated into the disrupted gene, revealed a nonubiquitous, sporadic distribution of PAR-2 in the SMG [10].

Anatomical context of Gpr172b

• We undertook this study to explore the importance of PAR-2 activation in 4 murine models of arthritis and to analyze the expression of PAR-2 in human arthritic synovium [2].
• Rac2-deficient neutrophils cannot chemotax, produce ROS, or degranulate upon G protein-coupled receptor (GPCR) activation [5].
• In order to investigate the dynamic mechanisms associated with GPCR signaling, the intracellular translocation of a green fluorescent protein-tagged PKD was analyzed by real-time visualization in fibroblasts and epithelial cells stimulated with bombesin, a GPCR agonist [11].
• It is the most abundant GPCR activated by LPA found in the small intestinal intraepithelial CD8+ cytotoxic T cells [12].
• These results indicate that PAR-2 present in the salivary glands mediates Ca(2+)-dependent fluid secretion, demonstrating potential usefulness of PAR-2 as a target for dry mouth treatment [10].

Associations of Gpr172b with chemical compounds

• Protein kinase D (PKD)/protein kinase C (PKC) mu is a serine/threonine protein kinase that can be activated by physiological stimuli like growth factors, antigen-receptor engagement and G protein-coupled receptor (GPCR) agonists via a phosphorylation-dependent mechanism that requires PKC activity [11].
• Furthermore, compared with the secretion in WT mice, PAR-2-mediated salivary secretion and Ca(2+) response were enhanced in mice lacking M(3) or both M(1) and M(3) mAChRs, in which mAChR-stimulated secretion and Ca(2+) response in acinar cells were severely impaired [10].
• PAR2 agonists caused delayed facilitation of sensitivity to capsaicin [3].
• PAR-2 Deficient CD4+ T Cells Exhibit Downregulation of IL-4 and Upregulation of IFN-gamma after Antigen Challenge in Mice [13].

References