Eukaryote initiation factor kinase

Wang, X., Flynn, A., Waskiewicz, A. J., Webb, B. L. J., Vries, R. G., Baines, I. A., Cooper, J., and Proud, C. G. (1998). The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol esters, cell stresses, and cytokines is mediated by distinct MAP kinase pathways. J. Biol. Chem. 273, 9373-9377. 

Many antibiotics, which inhibit protein synthesis, do not bind to ribosomes but block any of a variety of vital chemical processes needed for growth. Among them are pseudomonic acid, which inhibits isoleucyl-tRNA synthetase from many gram-positive bacteria.1111/VV Rapamycin, best known as an immunosuppressant (Box 9-F), inhibits phosphoinositide-3-kinase and also phosphorylation of the cap-binding protein 4G, a component of the eukaryotic initiation factor complex (Fig. 29-11 ).ww The bacterial enzyme peptide deformylase, which is absent from the human body, has been suggested as a target for design of synthetic antibiotics. 01... 

Fig. 4.3 Mechanism of action of sirolimus. Sirolimus readily diffuses into the cytoplasm of the target cells where it binds to immunophilins (FK506-BP). The sirolimus-immunophilin complex does not inhibit calcineurin activity instead it binds to the mTOR. The sirolimus-immunophilin-mTOR complex stops the cell cycle progression from G1 to S phase. The targets of sirolimus include the eukaryotic initiation factor (eIF-4F), 70-kDa S6 protein kinase (p70S6 K) and several cyclin-dependent kinases (cdk). As a consequence, it blocks downstream signaling pathway initiated after activation of IL-2 receptors, resulting in blockage of T-cell proliferation (see Color Insert)...

Translation can be inhibited through the phosphorylation of eukaryote initiation factor 2 (eIF2) by dsRNA-dependent PK (activated by viral dsRNA as a consequence of viral infection), by hemin-inhibited PK (activated in the absence of hemin in reticulocytes) and by GCN2 kinase (general control non-derepressible kinase) (activated by amino acid starvation and excess free tRNA). Phosphorylation of RNA polymerase II is a key process in the regulation of transcription (Chapter 9). 

Shi, Y, Vattem, K.M., Sood, R., An, J., Liang, J., Stramm, L. and Wek, R.C. (1998) Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. Mol. Cell Biol. 18, 7499-7509. 

Nitric oxide reacts with Fen(M4PyTPP), where M4PyTPP = meso-4-pyridyltriphenyl-porphyrinate, to form two nitrosyl complexes, identified by IR spectroscopy.298 The resonance Raman spectrum of the NO-bound ferric derivative of HbN (a haemoglobin from Mycobacterium tuberculosis) showed a shift of vNO from 1914 cm-1 to 1908 cm-1 on forming the B10 Tyr - Phe mutant.299 The resonance Raman spectrum of the iron(II)-NO complex of the haem-regulated eukaryotic initiation factor 2a kinase (HRI) is consistent with a... 

Padyana AK. Qiu H, RoU-Mecak A, Hinnebusch AG, Burley SK. 2005. Structural basis for autoinhibition and mutational activation of eukaryotic initiation factor 2a protein kinase GCN2. J Biol Chem 280 29289-29299. 

Sharp JW, Ross-Inta CM, Hao S, Rudell JB, Gietzen DW. 2006. Co-localization of phosphorylated extracellular signal-related protein kinases 1/2 (ERK 1/2) and phosphorylated eukaryotic initiation factor 2a (eIF2a) in response to a threonine-devoid diet. J Comp Neurol 494 485-494. (Gives A-P dimension and location of APC cells that may be the primary sensory cells for lAA deficiency)... 

Morimoto, H. et al., Okadaic acid induces apoptosis through double-stranded RNA-dependent protein kinase/eukaryotic initiation factor-2a pathway in human osteoblastic MG63 cells, J. Biochem., 136, 433, 2004. 

Meurs EF, Watanabe Y, Kadereit S, Barber GN, Katze MG, Chong K, Williams BR, Hovanessian AG (1992) Constitutive expression of human double-stranded RNA-activated p68 kinase in murine cells mediates phosphorylation of eukaryotic initiation factor 2 and partial resistance to encephalomyo-carditis virus growth. J Virol 66 5804-5814... 

LEVIN, D. and LONDON, I.M. Regulation of protein synthesis Activation by double-stranded RNA of a protein kinase that phosphorylates eukaryotic initiation factor 2. Proc. Natl. 

There are four main canonical response pathways to manage unfolded proteins via unfolded protein response (UPR) signaling and HSP. PKR-related ER kinase (PERK) is one of receptors to detect ER stress at the ER lumen, which normally binds with BIP (GRP78) (Samali and 2010). When unfolded protein binds to BIP and dissociates from BIP/PERK complex, PERK becomes active and phosphorylates eukaryotic initiation factor 2 initiation factor 2a (eIF2) (Samali etal. 2010). Phosphory-... 

Ernst, V., Levin, D. H., Leroux, A., and London, I. M., 1980, Site-specific phosphorylation of the a-subunit of eukaryotic initiation factor eIF-2 by the heme-regulated and double-stranded RNA-activated eIF-2a kinases from rabbit reticulocyte lysates, Proc. Natl. Acad. Sci. USA 77 1286. 

Jagus, R., and Safer, B., 1981a, Activity of eukaryotic initiation factor 2 is modified by processes distinct from phosphorylation. Activities of eukaryotic initiation factor 2 and eukaryotic initiation factor 2a kinase in lysate gel filtered under different conditions, J. Biol. Chem. 256 1317. 

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