Regulation of translation elongation and phosphorylation of eEF2 in rat pancreatic acini.
While pancreatic protein synthesis and the initiation of translation are regulated by hormones and neurotransmiters, whether the elongation process is also regulated is unknown. Stimulatory doses of cholecystokinin (CCK) (100 pM), bombesin (10 nM), and carbachol (10 microM) increased elongation rates (measured as ribosomal half-transit time) in pancreatic acini in vitro. At the same time these secretagogues reduced elongation factor 2 (eEF2) phosphorylation, the main factor known to regulate elongation, and increased the phosphorylation of the eEF2 kinase. The mTOR inhibitor rapamycin reversed the dephosphorylation of eEF2 induced by CCK, as did treatment with the p38 MAPK inhibitor SB202190, the MEK inhibitor PD98059, and the phosphatase inhibitor calyculin A. Neither rapamycin, SB202190, PD98059 nor calyculin A had an effect on CCK mediated eEF2 kinase phosphorylation. Translation elongation in pancreatic acinar cells is likely regulated by eEF2 through the mTOR, p38, and MEK pathways, and modulated through PP2A.
Sans
Maria Dolors
MD
Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, MI 48109-0622, USA. mdsansg@umich.edu
Xie
Qun
Q
Williams
John A
JA
D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D054736:Elongation Factor 2 Kinase; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008387:Marine Toxins; D010080:Oxazoles / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism*; D020652:Peptide Elongation Factor 2 / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013997:Time Factors
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D008387:Marine Toxins; D010080:Oxazoles; D020652:Peptide Elongation Factor 2; D010455:Peptides; D011725:Pyridines; C059041:calyculin A; D002217:Carbachol; D002766:Cholecystokinin; D000242:Cyclic AMP; C517691:Eef2k protein, rat; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D054736:Elongation Factor 2 Kinase; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; D001839:Bombesin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D020123:Sirolimus