Regulation of protein synthesis.
A system of translational control in eukaryotes consists of (a) a proinhibitor and (b) an inhibitor of polypeptide chain initiation. The inhibitor (active eIF-2 kinase), a cAMP-independent protein kinase, catalyzes the phosphorylation by ATP of the small subunit of the polypeptide chain initiation factor eIF-2. This blocks the interaction of eIF-2 with eIF-2 stimulating protein (ESP) without which eIF-2 is unable to form an initiation complex, a prerequisite for translation. Our observations are consistent with the view that the proinhibitor (inactive eIF-2 kinase) is converted to the inhibitor by phosphorylation catalyzed by a cAMP-dependent protein kinase. This is analogous to the conversion of inactive phosphorylase kinase to active phosphorylase kinase. As in the case of phosphorylase kinase and phosphorylase, the modification of activity produced by phosphorylation of eIF-2 kinase and eIF-2 itself is probably reversed by dephosphorylation catalyzed by specific protein phosphatases (see diagram in Fig. 12) but no evidence bearing on this aspect of the problem is yet available. Hemin inhibits the cAMP-induced dissociation of the regulatory and catalytic subunits of cAMP-dependent protein kinase by binding to the regulatory subunit of the enzyme and blocking, through an allosteric effect, the binding of cAMP. Thus, hemin prevents the activation of eIF-2 kinase by inhibiting the cAMP-dependent protein kinase.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005914:Globins / Q000096:biosynthesis*; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000494:pharmacology*; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects; D010448:Peptide Initiation Factors / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism
D010448:Peptide Initiation Factors; D047428:Protein Kinase Inhibitors; D006418:Heme; D006427:Hemin; D000255:Adenosine Triphosphate; D005914:Globins; D000242:Cyclic AMP; D011494:Protein Kinases