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Secreted Phospholipase A2 Type IIA (sPLA2-IIA) Activates Integrins in an Allosteric Manner

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Protein Reviews

Part of the book series: Advances in Experimental Medicine and Biology ((PROTRE,volume 925))

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.

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Abbreviations

FKN-CD:

the chemokine domain of fractalkine

IL:

interleukin

NF-kB:

nuclear factor kappa-light-chain-enhancer of activated B cells

RGD:

Arg-Gly-Asp

sPLA2-IIA:

Secreted phospholipase A2 type IIA

TNF:

Tumor necrosis factor.

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The authors declare that they have no conflicts of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Authors and Affiliations

  1. Department of Dermatology, Biochemistry and Molecular Medicine, UC Davis School of Medicine, Research III Suite 3300, 4645 Second Avenue, Sacramento, CA, 95817, USA

    Yoshikazu Takada

  2. 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

    Yoshikazu Takada

  3. Department of Clinical Immunology and Rheumatology, The Tazuke-Kofukai Medical Research Institute, Kitano Hospital, 2-4-20 Ohgimachi, Kita-ku, Osaka, 530-8480, Japan

    Masaaki Fujita

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  1. Yoshikazu Takada
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  2. Masaaki Fujita
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Correspondence to Yoshikazu Takada .

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Editors and Affiliations

  1. Biochem and Mol Biol, Baylor College of Medicine, Houston, Texas, USA

    M. Zouhair Atassi

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Takada, Y., Fujita, M. (2016). Secreted Phospholipase A2 Type IIA (sPLA2-IIA) Activates Integrins in an Allosteric Manner. In: Atassi, M. (eds) Protein Reviews. Advances in Experimental Medicine and Biology(), vol 925. Springer, Singapore. https://doi.org/10.1007/5584_2016_95

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