Western Blot Positive WB detected in: HepG2 whole cell lysate, A549 whole cell lysate, HEK293 whole cell lysate, Rat heart tissue, Rat lung tissue All lanes: EIF2AK1 antibody at 3μg/ml Secondary Goat polyclonal to rabbit IgG at 1/50000 dilution Predicted band size: 72 kDa Observed band size: 72 kDa
Immunohistochemistry of paraffin-embedded human spleen tissue using CSB-PA007510LA01HU at dilution of 1:100
Immunohistochemistry of paraffin-embedded human testis tissue using CSB-PA007510LA01HU at dilution of 1:100
Immunofluorescent analysis of HepG2 cells using CSB-PA007510LA01HU at dilution of 1:100 and Alexa Fluor 488-congugated AffiniPure Goat Anti-Rabbit IgG(H+L)
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貨期:
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用途:
For Research Use Only. Not for use in diagnostic or therapeutic procedures.
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress conditions. Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as heme deficiency, oxidative stress, osmotic shock, mitochondrial dysfunction and heat shock. EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming. Acts as a key sensor of heme-deficiency: in normal conditions, binds hemin via a cysteine thiolate and histidine nitrogenous coordination, leading to inhibit the protein kinase activity. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell: heme depletion relieves inhibition and stimulates kinase activity, activating the ISR. Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions. In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties. It thereby plays an essential protective role for RBC survival in anemias of iron deficiency. Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes. May also regulate endoplasmic reticulum (ER) stress during acute heme-deficient conditions. Also activates the ISR in response to mitochondrial dysHRI/EIF2AK1 protein kinase activity is activated upon binding to the processed form of DELE1 (S-DELE1), thereby promoting the ATF4-mediated reprogramming.
基因功能參考文獻(xiàn):
Activation of HRI is mediated by Hsp90 during stress through modulation of the HRI-Hsp90 complex PMID: 30170366
Taken together, these results suggest HRI as a potential therapeutic target for hemoglobinopathies. PMID: 30026227
data suggests that glutamatergic stimulation induces HRI activation by NO to trigger GluN2B expression and this process would be relevant to maintain postsynaptic activity in cortical neurons PMID: 27557499
The antiviral kinase PKR plays a critical role in controlling HCMV replication. PMID: 27974558
structural and functional stability of HRI PMID: 27888007
Infection-associated functions of HRI (an eIF2alpha kinase) are independent of its activity as a regulator of protein synthesis. PMID: 23874749
During lead-stress, the regulation of hHRI mRNA translation is mediated through its 5'-untranslated region (UTR) that interacts with specific trans-acting factors. PMID: 23357686
Dephosphorylation of eIF2alpha, specifically in the cortex, is both correlated with and necessary for normal memory consolidation. PMID: 23392680
eukaryotic initiation factor 2alpha kinase is a protagonist of heme-mediated translational control of CYP2B enzymes and a modulator of basal endoplasmic reticulum stress tone. PMID: 20071449
autophosphorylation of Thr485 is essential for the hyperphosphorylation and activation of HRI and is required for the acquisition of the eIF2alpha kinase activity PMID: 12767237
These data establish for the first time, the possible mechanisms of regulation of hHRI gene expression under normal physiological condition, hemin exposure and stress. PMID: 19133234
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蛋白家族:
Protein kinase superfamily, Ser/Thr protein kinase family, GCN2 subfamily
組織特異性:
Expressed predominantly in erythroid cells. Expressed at much lower levels in hepatocytes (at protein level).