Takada Yoshikazu, Fujita Masaaki
Department of Dermatology, Biochemistry and Molecular Medicine, UC Davis School of Medicine, Research III Suite 3300, 4645 Second Avenue, Sacramento, CA, 95817, USA.
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.
Adv Exp Med Biol. 2017;925:103-115. doi: 10.1007/5584_2016_95.
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.
分泌型磷脂酶A2 IIA型（sPLA2-IIA）是一种公认的促炎蛋白，一直是药物研发的主要靶点。然而，其信号传导作用机制尚未完全明确。我们之前发现，sPLA2-IIA在人体内与整合素αvβ3和α4β1结合，且这种相互作用在sPLA2-IIA的信号传导作用中发挥作用。我们最近的研究发现，sPLA2-IIA通过直接结合整合素新发现的结合位点（位点2）以变构方式激活整合素，该位点不同于经典的RGD结合位点（位点1）。sPLA2-IIA诱导的整合素激活可能与sPLA2-IIA的信号传导作用有关。由于sPLA2-IIA除了在类风湿性滑液中高浓度存在外，还存在于正常人泪液中，因此sPLA2-IIA介导的白细胞上整合素激活可能参与正常和病理条件下的免疫反应。
