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Mechanism of action of an eukaryotic initiation factor-2 (eIF-2) associated 67 kDa glycoprotein (p67) and an eIF-2 kinase (dsI). 1994

A Chakraborty, and D Saha, and A Bose, and R E Hileman, and M Chatterjee, and N K Gupta
Department of Chemistry, University of Nebraska, Lincoln 68588-0304.

Mechanism of regulation of eIF-2 alpha-subunit phosphorylation by dsI and p67 was studied. The results are as follows: (1) At low dsI concentration, p67 protected equimolar concentration of eIF-2. (2) At high dsI concentration, dsI efficiently phosphorylated eIF-2 alpha-subunit even when equimolar concentrations of both p67 and eIF-2 were present. Significantly increased p67 concentration was necessary to protect eIF-2 alpha-subunit at high dsI concentration. (3) dsI was also phosphorylated as it phosphorylated eIF-2 alpha-subunit. p67 inhibited both eIF-2 alpha-subunit and dsI phosphorylation similarly. (4) Although the [32P]-labelled dsI formed during the reaction could be effectively chased upon subsequent addition of excess unlabelled eIF-2 and ATP, the [32P] labelled eIF-2 formed under identical conditions, retained most of the radioactivity. (5) dsI coimmunoprecipitated with three subunit eIF-2 and p67 inhibited this coimmunoprecipitation reaction. It has been proposed: Three subunit eIF-2 and free p67 are in equilibrium with eIF-2 bound to p67 and, eIF-2.p67 complex is resistant to dsI phosphorylation. Activated dsI is already phosphorylated. At high concentration, dsI(P) can bind to free three subunit eIF-2 and form eIF-2.dsI(P) complex. dsI(P) in this complex then transfers its phosphoryl residue to eIF-2 and forms eIF-2 alpha(P) in an irreversible reaction. In a subsequent reaction, unphosphorylated dsI is autophosphorylated using [gamma 32P]-ATP and the cycle continues. Inhibition of eIF-2 alpha-subunit phosphorylation by p67 blocks this phosphorylation cycle and consequent dsI phosphorylation.

UI MeSH Term Description Entries
D008970 Molecular Weight The sum of the weight of all the atoms in a molecule. Molecular Weights,Weight, Molecular,Weights, Molecular
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D006023 Glycoproteins Conjugated protein-carbohydrate compounds including MUCINS; mucoid, and AMYLOID glycoproteins. C-Glycosylated Proteins,Glycosylated Protein,Glycosylated Proteins,N-Glycosylated Proteins,O-Glycosylated Proteins,Glycoprotein,Neoglycoproteins,Protein, Glycosylated,Proteins, C-Glycosylated,Proteins, Glycosylated,Proteins, N-Glycosylated,Proteins, O-Glycosylated
D000626 Aminopeptidases A subclass of EXOPEPTIDASES that act on the free N terminus end of a polypeptide liberating a single amino acid residue. EC 3.4.11. Aminopeptidase
D015852 Eukaryotic Initiation Factor-2 Eukaryotic initiation factor of protein synthesis. In higher eukaryotes the factor consists of three subunits: alpha, beta, and gamma. As initiation proceeds, eIF-2 forms a ternary complex with Met-tRNAi and GTP. EIF-2,Peptide Initiation Factor EIF-2,EIF-2 alpha,EIF-2 beta,EIF-2 gamma,EIF-2alpha,EIF-2beta,EIF-2gamma,EIF2,Eukaryotic Initiation Factor-2, alpha Subunit,Eukaryotic Initiation Factor-2, beta Subunit,Eukaryotic Initiation Factor-2, gamma Subunit,Eukaryotic Peptide Initiation Factor-2,EIF 2,EIF 2 alpha,EIF 2 beta,EIF 2 gamma,EIF 2alpha,EIF 2beta,EIF 2gamma,Eukaryotic Initiation Factor 2,Eukaryotic Initiation Factor 2, alpha Subunit,Eukaryotic Initiation Factor 2, beta Subunit,Eukaryotic Initiation Factor 2, gamma Subunit,Eukaryotic Peptide Initiation Factor 2,Initiation Factor-2, Eukaryotic,Peptide Initiation Factor EIF 2
D017346 Protein Serine-Threonine Kinases A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. Protein-Serine-Threonine Kinases,Serine-Threonine Protein Kinase,Serine-Threonine Protein Kinases,Protein-Serine Kinase,Protein-Serine-Threonine Kinase,Protein-Threonine Kinase,Serine Kinase,Serine-Threonine Kinase,Serine-Threonine Kinases,Threonine Kinase,Kinase, Protein-Serine,Kinase, Protein-Serine-Threonine,Kinase, Protein-Threonine,Kinase, Serine-Threonine,Kinases, Protein Serine-Threonine,Kinases, Protein-Serine-Threonine,Kinases, Serine-Threonine,Protein Kinase, Serine-Threonine,Protein Kinases, Serine-Threonine,Protein Serine Kinase,Protein Serine Threonine Kinase,Protein Serine Threonine Kinases,Protein Threonine Kinase,Serine Threonine Kinase,Serine Threonine Kinases,Serine Threonine Protein Kinase,Serine Threonine Protein Kinases
D019892 eIF-2 Kinase A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis. Protein Kinase PKR,Protein Kinase, RNA Activated,RNA-Dependent Protein Kinase,p68 Kinase,DAI Protein Kinase,DSRNA-Dep Protein Kinase,Double Stranded RNA-Dependent Kinase (dsl),Double Stranded RNA-Dependent eIF-2 alpha Protein Kinase,Eukaryotic Initiation Factor 2alpha Kinase,Heme Controlled Repressor,Heme-Controlled Inhibitor,Heme-Controlled Translational Repressor,Heme-Regulated eIF-2alpha Kinase,Hemin Controlled Repressor,Hemin-Controlled Translational Repressor,P68 Protein Kinase,Self-Phosphorylating Protein Kinase,TIK Kinase,dsRNA-Activated Inhibitor,eIF-2alpha Kinase,eRF, eIF-2 Recycling Factor,p65 Kinase,Controlled Repressor, Heme,Controlled Repressor, Hemin,DSRNA Dep Protein Kinase,Double Stranded RNA Dependent eIF 2 alpha Protein Kinase,Heme Controlled Inhibitor,Heme Controlled Translational Repressor,Heme Regulated eIF 2alpha Kinase,Hemin Controlled Translational Repressor,Inhibitor, Heme-Controlled,Inhibitor, dsRNA-Activated,Kinase PKR, Protein,Kinase, DAI Protein,Kinase, DSRNA-Dep Protein,Kinase, Heme-Regulated eIF-2alpha,Kinase, P68 Protein,Kinase, RNA-Dependent Protein,Kinase, Self-Phosphorylating Protein,Kinase, TIK,Kinase, eIF-2,Kinase, eIF-2alpha,Kinase, p65,Kinase, p68,PKR, Protein Kinase,Protein Kinase, DAI,Protein Kinase, DSRNA-Dep,Protein Kinase, P68,Protein Kinase, RNA-Dependent,Protein Kinase, Self-Phosphorylating,RNA Dependent Protein Kinase,Repressor, Heme Controlled,Repressor, Heme-Controlled Translational,Repressor, Hemin Controlled,Repressor, Hemin-Controlled Translational,Self Phosphorylating Protein Kinase,Translational Repressor, Heme-Controlled,Translational Repressor, Hemin-Controlled,dsRNA Activated Inhibitor,eIF 2 Kinase,eIF 2alpha Kinase,eIF-2alpha Kinase, Heme-Regulated,eRF, eIF 2 Recycling Factor
D063208 Methionyl Aminopeptidases Aminopeptidases that remove METHIONINE from the amino-terminus of a peptide chain, such as the initiator METHIONINE found on nascent peptide chains. Methionyl Aminopeptidase,N-Terminal Methionine-Specific Peptidase,Peptidase M,Aminopeptidase, Methionyl,Aminopeptidases, Methionyl,Methionine-Specific Peptidase, N-Terminal,N Terminal Methionine Specific Peptidase

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