Secreted phospholipase A2 type IIA (sPLA2-IIA) activates integrins in an allosteric manner

Yoshikazu Takada, Masaaki Fujita

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Scopus citations

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.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages103-115
Number of pages13
Volume925
DOIs
StatePublished - 2017

Publication series

NameAdvances in Experimental Medicine and Biology
Volume925
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

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Keywords

  • Allosteric site
  • Docking simulation
  • Integrin activation
  • Secreted phospholipase A2 type IIA (sPLA2-IIA)

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Takada, Y., & Fujita, M. (2017). Secreted phospholipase A2 type IIA (sPLA2-IIA) activates integrins in an allosteric manner. In Advances in Experimental Medicine and Biology (Vol. 925, pp. 103-115). (Advances in Experimental Medicine and Biology; Vol. 925). Springer New York LLC. https://doi.org/10.1007/5584_2016_95