title: Secreted Phospholipase A2 Type IIA (sPLA2-IIA) Activates Integrins in an Allosteric Manner.
abstract: Secreted phospholipase A2 type IIA (sPLA2-IIA) is a well-established pro-inflammatory protein and has been a major target for drug discovery. However, the mechanism of its signaling action has not been fully understood. We previously found that sPLA2-IIA binds to integrins αvβ3 and α4β1 in human and that this interaction plays a role in sPLA2-IIA's signaling action. Our recent studies found that sPLA2-IIA activates integrins in an allosteric manner through direct binding to a newly identified binding site of integrins (site 2), which is distinct from the classical RGD-binding site (site 1). The sPLA2-IIA-induced integrin activation may be related to the signaling action of sPLA2-IIA. Since sPLA2-IIA is present in normal human tears in addition to rheumatoid synovial fluid at high concentrations the sPLA2-IIA-mediated integrin activation on leukocytes may be involved in immune responses in normal and pathological conditions.
authors.affiliation: Department of Dermatology, Biochemistry and Molecular Medicine, UC Davis School of Medicine, Research III Suite 3300, 4645 Second Avenue, Sacramento, CA, 95817, USA. ytakada@ucdavis.edu.|The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 11031, Taiwan, Republic of China. ytakada@ucdavis.edu.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Takada
authors.affiliation: Department of Clinical Immunology and Rheumatology, The Tazuke-Kofukai Medical Research Institute, Kitano Hospital, 2-4-20 Ohgimachi, Kita-ku, Osaka, 530-8480, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Fujita
mesh_terms: D000494:Allosteric Regulation; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001665:Binding Sites; D005786:Gene Expression Regulation; D054501:Group II Phospholipases A2 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006801:Humans; D039041:Integrin alpha4beta1 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D039302:Integrin alphaVbeta3 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D062105:Molecular Docking Simulation; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction / Q000276:immunology*; D013582:Synovial Fluid / Q000737:chemistry / Q000276:immunology; D013666:Tears / Q000737:chemistry / Q000276:immunology
chemical_list: D039041:Integrin alpha4beta1; D039302:Integrin alphaVbeta3; D054501:Group II Phospholipases A2; C516287:PLA2G2A protein, human
keywords: Allosteric site; Docking simulation; Integrin activation; Secreted phospholipase A2 type IIA (sPLA2-IIA)