3u8i Citations

Selective inhibition of human group IIA-secreted phospholipase A2 (hGIIA) signaling reveals arachidonic acid metabolism is associated with colocalization of hGIIA to vimentin in rheumatoid synoviocytes.

J Biol Chem 288 15269-79 (2013)
Related entries: 3u8b, 3u8d, 3u8h

Cited: 17 times
EuropePMC logo PMID: 23482564

Abstract

Human group IIA secreted phospholipase A2 (hGIIA) promotes tumor growth and inflammation and can act independently of its well described catalytic lipase activity via an alternative poorly understood signaling pathway. With six chemically diverse inhibitors we show that it is possible to selectively inhibit hGIIA signaling over catalysis, and x-ray crystal structures illustrate that signaling involves a pharmacologically distinct surface to the catalytic site. We demonstrate in rheumatoid fibroblast-like synoviocytes that non-catalytic signaling is associated with rapid internalization of the enzyme and colocalization with vimentin. Trafficking of exogenous hGIIA was monitored with immunofluorescence studies, which revealed that vimentin localization is disrupted by inhibitors of signaling that belong to a rare class of small molecule inhibitors that modulate protein-protein interactions. This study provides structural and pharmacological evidence for an association between vimentin, hGIIA, and arachidonic acid metabolism in synovial inflammation, avenues for selective interrogation of hGIIA signaling, and new strategies for therapeutic hGIIA inhibitor design.

Reviews - 3u8i mentioned but not cited (1)

  1. Structural and Functional Aspects of Targeting the Secreted Human Group IIA Phospholipase A2. Kim RR, Chen Z, Mann TJ, Bastard K, F Scott K, Church WB. Molecules 25 E4459 (2020)

Articles - 3u8i mentioned but not cited (4)

  1. Selective inhibition of human group IIA-secreted phospholipase A2 (hGIIA) signaling reveals arachidonic acid metabolism is associated with colocalization of hGIIA to vimentin in rheumatoid synoviocytes. Lee LK, Bryant KJ, Bouveret R, Lei PW, Duff AP, Harrop SJ, Huang EP, Harvey RP, Gelb MH, Gray PP, Curmi PM, Cunningham AM, Church WB, Scott KF. J. Biol. Chem. 288 15269-15279 (2013)
  2. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)
  3. Mechanistic exploration of Yiqi Liangxue Shengji prescription on restenosis after balloon injury by integrating metabolomics with network pharmacology. Mao T, Xie L, Guo Y, Ji X, Wan J, Cui X, Fan Q, Liu W, Wang S, Han W, Lin Q, Jia W. Pharm Biol 61 1260-1273 (2023)
  4. Untargeted lipidomic analysis and network pharmacology for parthenolide treated papillary thyroid carcinoma cells. Huang LT, Li TJ, Li ML, Luo HY, Wang YB, Wang JH. BMC Complement Med Ther 23 130 (2023)


Reviews citing this publication (3)

  1. Human Group IIA Phospholipase A2-Three Decades on from Its Discovery. Scott KF, Mann TJ, Fatima S, Sajinovic M, Razdan A, Kim RR, Cooper A, Roohullah A, Bryant KJ, Gamage KK, Harman DG, Vafaee F, Graham GG, Church WB, Russell PJ, Dong Q, de Souza P. Molecules 26 7267 (2021)
  2. Secreted Phospholipases A2 - not just Enzymes: Revisited. Ivanušec A, Šribar J, Križaj I. Int J Biol Sci 18 873-888 (2022)
  3. Secretory Phospholipases A2, from Snakebite Envenoming to a Myriad of Inflammation Associated Human Diseases-What Is the Secret of Their Activity? Tonello F. Int J Mol Sci 24 1579 (2023)

Articles citing this publication (9)

  1. Reduction in the desaturation capacity of the liver in mice subjected to high fat diet: Relation to LCPUFA depletion in liver and extrahepatic tissues. Valenzuela R, Barrera C, Espinosa A, Llanos P, Orellana P, Videla LA. Prostaglandins Leukot. Essent. Fatty Acids 98 7-14 (2015)
  2. Down-regulation of survivin alleviates experimental arthritis. Andersson KM, Svensson MN, Erlandsson MC, Jonsson IM, Bokarewa MI. J. Leukoc. Biol. 97 135-145 (2015)
  3. Discovery of novel secretory phospholipase A2 inhibitors using virtual screen. Qiu S, Chen F, Liu Y, Lai L. Chem Biol Drug Des 84 216-222 (2014)
  4. Molecular dynamics simulations reveal structural insights into inhibitor binding modes and functionality in human Group IIA phospholipase A2. Kim RR, Malde AK, Nematollahi A, Scott KF, Church WB. Proteins 85 827-842 (2017)
  5. A Representative GIIA Phospholipase A2 Activates Preadipocytes to Produce Inflammatory Mediators Implicated in Obesity Development. Leiguez E, Motta P, Maia Marques R, Lomonte B, Sampaio SV, Teixeira C. Biomolecules 10 (2020)
  6. In Silico, In Vitro, and In Vivo Analysis of Tanshinone IIA and Cryptotanshinone from Salvia miltiorrhiza as Modulators of Cyclooxygenase-2/mPGES-1/Endothelial Prostaglandin EP3 Pathway. Saviano A, De Vita S, Chini MG, Marigliano N, Lauro G, Casillo GM, Raucci F, Iorizzi M, Hofstetter RK, Fischer K, Koeberle A, Werz O, Maione F, Bifulco G. Biomolecules 12 99 (2022)
  7. Motion lubrication suppressed mechanical activation via hydrated fibrous gene patch for tendon healing. Xiang L, Liang J, Wang Z, Lin F, Zhuang Y, Saiding Q, Wang F, Deng L, Cui W. Sci Adv 9 eadc9375 (2023)
  8. Multimodal regulation of the osteoclastogenesis process by secreted group IIA phospholipase A2. Mangini M, D'Angelo R, Vinciguerra C, Payré C, Lambeau G, Balestrieri B, Charles JF, Mariggiò S. Front Cell Dev Biol 10 966950 (2022)
  9. Structural basis for functional selectivity and ligand recognition revealed by crystal structures of human secreted phospholipase A2 group IIE. Hou S, Xu T, Xu J, Qu L, Xu Y, Chen L, Liu J. Sci Rep 7 10815 (2017)