Possible involvement of the 90-kDa heat shock protein in the regulation of protein synthesis.
The heme-sensitive eukaryotic initiation factor (eIF)-2 alpha kinase regulates translational activity in reticulocytes by phosphorylation of the smallest subunit of eukaryotic peptide initiation factor 2, eIF-2. Highly purified preparations of the kinase contain an abundant 90-kDa polypeptide which appears to modulate the activity of the enzyme. The physical properties and structural characteristics of the reticulocyte 90-kDa peptide are similar to those of the 90-kDa heat shock protein (hsp 90) from HeLa and other mammalian cells. The reticulocyte and HeLa cell proteins are shown to be immunologically cross-reactive. A direct comparison of the two proteins by one-dimensional peptide mapping of large peptides generated by limited proteolysis and by reversed-phase high performance liquid chromatography analysis of tryptic peptides indicates that they represent the same protein species. Like the 90-kDa reticulocyte protein, HeLa cell hsp 90 causes increased eIF-2 alpha phosphorylation by the heme-sensitive kinase and is a potent inhibitor of protein synthesis in the reticulocyte lysate system. A potential mechanism for the latter inhibition is inferred. These results implicate hsp 90 in the regulation of protein synthesis via its interaction with and perhaps regulation of the heme-sensitive kinase and phosphorylation of eIF-2 alpha.
Rose
D W
DW
Clayton Foundation Biochemical Institute, University of Texas, Austin 78712.
Welch
W J
WJ
Kramer
G
G
Hardesty
B
B
D000818:Animals; D002474:Cell-Free System; D003429:Cross Reactions; D015852:Eukaryotic Initiation Factor-2; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000276:immunology / Q000502:physiology*; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010449:Peptide Mapping; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011817:Rabbits; D012156:Reticulocytes; D019892:eIF-2 Kinase
D015852:Eukaryotic Initiation Factor-2; D006360:Heat-Shock Proteins; D010448:Peptide Initiation Factors; D011506:Proteins; D011494:Protein Kinases; D019892:eIF-2 Kinase