1. Secreted Phospholipase A2 Type IIA (sPLA2-IIA) Activates Integrins in an Allosteric Manner.
- Author
-
Takada Y and Fujita M
- Subjects
- Allosteric Regulation, Arthritis, Rheumatoid genetics, Arthritis, Rheumatoid immunology, Arthritis, Rheumatoid pathology, Binding Sites, Gene Expression Regulation, Group II Phospholipases A2 genetics, Group II Phospholipases A2 immunology, Humans, Integrin alpha4beta1 genetics, Integrin alpha4beta1 immunology, Integrin alphaVbeta3 genetics, Integrin alphaVbeta3 immunology, Molecular Docking Simulation, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Synovial Fluid chemistry, Synovial Fluid immunology, Tears chemistry, Tears immunology, Group II Phospholipases A2 chemistry, Integrin alpha4beta1 chemistry, Integrin alphaVbeta3 chemistry, Signal Transduction immunology
- 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.
- Published
- 2017
- Full Text
- View/download PDF