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. 2022 Aug 30;9:961027. doi: 10.3389/fmed.2022.961027

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Copyright © 2022 Khaledi, Sameni, Yahyazade, Radandish, Owlia, Bagheri, Afkhami, Mahjoor, Esmaelpour, Kohansal and Aghaei.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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IL-6 signaling pathways. IL-6 requires two receptors, the IL-6R and the gp130, to begin signaling. IL-6 (classic signaling) binds to either fluid- or membrane-bound IL-6R (SIL-6R, trans-signaling). In two modalities of IL-6R signaling, a hexamer complex with gp130 is formed. The JAK–MAPK route and the JAK–STAT3 pathway are both used by IL-6 to transfer signaling. JAK kinases phosphorylate tyrosine in the cytoplasmic region of gp130, which promotes STAT3 phosphorylation and causes homodimerization, which works as a transcription factor in the nucleus.