Heme-regulated inhibitor kinase

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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.

[edit] 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).

[edit] 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