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. Author manuscript; available in PMC: 2013 Jan 6.
Published in final edited form as: Circ Res. 2012 Jan 6;110(1):174–189. doi: 10.1161/CIRCRESAHA.111.243212

Figure 2.

Figure 2

Signal transduction events that link ER stress to inflammation. Unfolded proteins in the ER cause release of IRE1, PERK, and ATF6. Once released, IRE1α binds TRAF2, activating signaling downstream kinases that activate NFκB and AP-1, causing expression of genes associated with inflammatory response. The intrinsic ribonuclease activity of IRE1α also results in production of XBP1, inducing production of inflammatory cytokines by enhancing TLR signaling and differentiation of B lymphocytes and dendritic cells. PERK activates its intrinsic kinase activity, causing phosphorylation of eIF2 and attenuation of translation of IκB, resulting in excess of NFκB moving to the nucleus and induces expression of genes involved in inflammatory pathways. Selective activation ATF4 by PERK induces production of inflammatory cytokines and regulates redox homeostasis. Activation of ATF6 also induces activation of NFκB. ATF6 can also induce production of XBP1 (not shown).