| http://purl.uniprot.org/citations/18635536 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18635536 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18635536 | http://www.w3.org/2000/01/rdf-schema#comment | "Secretory phospholipase A2 group IIA (sPLA2-IIA) plays an important role in the pathogenesis of inflammatory diseases. Catalytic activity of this enzyme that generates arachidonic acid is a major target for development of anti-inflammatory agents. Independent of its catalytic activity, sPLA2-IIA induces pro-inflammatory signals in a receptor-mediated mechanism (e.g. through the M-type receptor). However, the M-type receptor is species-specific: sPLA2-IIA binds to the M-type receptor in rodents and rabbits, but not in human. Thus sPLA2-IIA receptors in human have not been established. Here we demonstrated that sPLA2-IIA bound to integrin alphavbeta3 at a high affinity (K(D)=2 x 10(-7) M). We identified amino acid residues in sPLA2-IIA (Arg-74 and Arg-100) that are critical for integrin binding using docking simulation and mutagenesis. The integrin-binding site did not include the catalytic center or the M-type receptor-binding site. sPLA2-IIA also bound to alpha4beta1. We showed that sPLA2-IIA competed with VCAM-1 for binding to alpha4beta1, and bound to a site close to those for VCAM-1 and CS-1 in the alpha4 subunit. Wild type and the catalytically inactive H47Q mutant of sPLA2-IIA induced cell proliferation and ERK1/2 activation in monocytic cells, but the integrin binding-defective R74E/R100E mutant did not. This indicates that integrin binding is required, but catalytic activity is not required, for sPLA2-IIA-induced proliferative signaling. These results suggest that integrins alphavbeta3 and alpha4beta1 may serve as receptors for sPLA2-IIA and mediate pro-inflammatory action of sPLA2-IIA, and that integrin-sPLA2-IIA interaction is a novel therapeutic target."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m804835200"xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m804835200"xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Akakura N."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Akakura N."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Ma Z."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Ma Z."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Takada Y."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Takada Y."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Hoogland C."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Hoogland C."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Wu C.Y."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Wu C.Y."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Lam K.S."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Lam K.S."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Liu F.T."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Liu F.T."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Takada Y.K."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Takada Y.K."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Saegusa J."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/author | "Saegusa J."xsd:string |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18635536 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |