Heme-regulated inhibitor kinase
- Heme-regulated inhibitor kinase
Heme-regulated inhibitor (HRI) kinase is a member of the eIF-2{alpha} kinase family. When heme concentrations are low in the RBC, it shuts off production of globin chains. This has the effectively keeps hemoglobin synthesis proportional to cellular resources.
Mechanism
Under normal cellular conditions, eIF-2{alpha} productively interacts with eIF-2B, giving rise to guanine-nucleotide exchange activity that is essential for protein translation. Low concentrations of heme activate Heme-Regulated Inhibitor Kinase, which phosphorylates the Serine-51 of eIF-2{alpha}, and makes its interaction with eIF-2B nonproductive(eIF-2{alpha} sequesters eIF-2B). This cascade is known to effect mammalian erythroid globin synthesis through HRI1P and HRI2P. Similar mechanisms exist for the cellular response to double stranded RNA(PKR), and endoplasmic reticulum stress(PERK).
References
Zhan K, et al. Phosphorylation of Eukaryotic Initiation Factor 2 by Heme-Regulated Inhibitor Kinase-Related Protein Kinases in Schizosaccharomyces pombe Is Important for Resistance to Environmental Stresses. Molecular and Cellular Biology, October 2002, p. 7134-7146, Vol. 22, No. 20
ee also
*EIF2AK1
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