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Secreted Phospholipase A2 Type IIA (sPLA2-IIA) Activates Integrins in an Allosteric Manner.
- Source :
-
Advances in experimental medicine and biology [Adv Exp Med Biol] 2017; Vol. 925, pp. 103-115. - Publication Year :
- 2017
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 0065-2598
- Volume :
- 925
- Database :
- MEDLINE
- Journal :
- Advances in experimental medicine and biology
- Publication Type :
- Academic Journal
- Accession number :
- 27864802
- Full Text :
- https://doi.org/10.1007/5584_2016_95