PGK1 modulates balance between pro- and anti-inflammatory cytokines by interacting with ITI-H4 - 28/03/23
Abstract |
Inter-α-trypsin inhibitor heavy chain 4 (ITI-H4) is one of the acute phase proteins and is mainly related with inflammatory diseases such as bacterial bloodstream infection and recurrent pregnancy loss (RPL). In a previous study, ITI-H4 was reported to be cleaved by kallikrein B1 (KLKB1) and its cleaved form induces the imbalance between pro- and anti-inflammatory cytokines. Therefore, in this study, putative substrates of ITI-H4 were isolated by immunoprecipitation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) analysis. Of those, phosphoglycerate kinase 1 (PGK1) was found to be a binding protein of ITI-H4. PGK1 increases the level of ITI-H4 expression and blocks the cleavage of ITI-H4 mediated by KLKB1. It also inhibits pro-inflammatory response by inhibiting the JAK2/STAT3 signaling pathway. Therefore, PGK1, a novel binding partner of ITI-H4, is expected to have cellular functions in the pathogenesis of ITI-H4-related inflammatory diseases.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | PGK1 is a novel binding partner of ITI-H4. |
• | PGK1 increases the protein level of ITI-H4 and blocks the cleavage of ITI-H4 by KLKB1. |
• | KLKB1 and PGK1 competitively bind to ITI-H4. |
• | Threonine phosphorylation of ITI-H4 is regulated by PGK1. |
• | PGK1 modulates pro- and anti-inflammatory response via the JAK2/STAT3 signaling pathway. |
Abbreviations : ITI-H4, RPL, BKD, KLKB1, MASP-1, PGK1, PGK2, HIF-1α, PDHK1, NFAT5, PPARγ, MALDI-TOF/MS, APS, DNAJC1, VEGF, IPTG, ICC, PBS, RT-PCR, ILF2, lncRNA, DDX5, ISGs, PP2A-Cβ, HSPA1B
Keywords : Inflammatory diseases, JAK2/STAT3 signaling pathway, Kinase, Mass spectrometry (MS), Recurrent pregnancy loss (RPL)
Plan
Vol 161
Article 114437- mai 2023 Retour au numéro
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