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. Author manuscript; available in PMC: 2015 May 1.
Published in final edited form as: Curr Opin Hematol. 2014 May;21(3):172–178. doi: 10.1097/MOH.0000000000000030

Fig. 1. Family of eIF2α kinase and the integrated stress response of eIF2αP signaling.

Fig. 1

(A) Protein structure of HRI. There are two heme binding domains in HRI, the N-terminus and the kinase insertion region. The Roman numerals above the gray regions denote the conserved kinase domains of eIF2α kinases. (B) Integrated stress response. In mammalian cells, there are four eIF2α kinases that are activated in response to four major stress, nutrient starvation, viral infection, heme deficiency and ER stress. Activated eIF2α kinases phosphorylate eIF2α and inhibit protein synthesis to prevent proteotoxocity of unfolded protein occurs in ER stress and globin inclusions in heme deficiency. In addition, eIF2αP selectively enhances the translation of ATF4 mRNA. ATF4 then initiates an adaptive gene expression to mitigate stress.