Regulation of protein synthesis by cholecystokinin in rat pancreatic acini involves PHAS-I and the p70 S6 kinase pathway

Gastroenterology. 1998 Sep;115(3):733-42. doi: 10.1016/s0016-5085(98)70153-2.


Background & aims: Cholecystokinin (CCK) stimulates protein synthesis in pancreatic acini at the translational level, although the signaling mechanisms involved remain uncharacterized. Two intermediates controlling translation are p70 S6 kinase and PHAS-I. We previously showed that CCK activates p70 S6K in pancreatic acini through phosphatidylinositol 3-kinase (PI 3K). In the present study we investigated the role of PI 3K, p70 S6K, and PHAS-I in mediating CCK-stimulated protein synthesis.

Methods: Protein synthesis was measured by [35S]methionine incorporation into pancreatic protein using acini from rats with streptozotocin-induced diabetes. p70 S6 K activity was measured. PHAS-I was identified by Western analysis. PHAS-I/eIF-4E association was measured as the amount of PHAS-I recovered after purification of translation factor eIF-4E by 7-methyl guanosine triphosphate-Sepharose.

Results: Rapamycin and PI 3K inhibitors, wortmannin and LY294002, blocked CCK-stimulated p70 S6K activity. Rapamycin inhibited basal protein synthesis and blocked the increase to all CCK concentrations. Wortmannin and LY294002 dose-dependently inhibited basal and CCK-stimulated protein synthesis and also blocked insulin-stimulated protein synthesis. CCK dose-dependently increased PHAS-I phosphorylation via a rapamycin- and LY294002-sensitive pathway and decreased the amount of PHAS-I associated with eIF-4E. Rapamycin and LY294002 eliminated this effect of CCK.

Conclusions: CCK stimulation of protein synthesis in pancreatic acini is sensitive to rapamycin and PI 3K inhibitors and involves PHAS-I phosphorylation and its association with eIF-4E.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Bombesin / pharmacology
  • Carbachol / pharmacology
  • Carrier Proteins*
  • Cholecystokinin / pharmacology*
  • Chromones / pharmacology
  • Diabetes Mellitus, Experimental / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Intracellular Signaling Peptides and Proteins
  • Kinetics
  • Male
  • Methionine / metabolism
  • Morpholines / pharmacology
  • Pancreas / cytology
  • Pancreas / metabolism*
  • Pancreas / pathology
  • Peptide Initiation Factors / metabolism
  • Phosphoproteins / metabolism*
  • Polyenes / pharmacology
  • Protein Biosynthesis*
  • Proteins / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Ribosomal Protein S6 Kinases / metabolism*
  • Sirolimus
  • Sulfur Radioisotopes
  • Tetradecanoylphorbol Acetate / pharmacology
  • Wortmannin


  • Androstadienes
  • Carrier Proteins
  • Chromones
  • Eif4ebp1 protein, rat
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Morpholines
  • Peptide Initiation Factors
  • Phosphoproteins
  • Polyenes
  • Proteins
  • Sulfur Radioisotopes
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Carbachol
  • Cholecystokinin
  • Methionine
  • Ribosomal Protein S6 Kinases
  • Tetradecanoylphorbol Acetate
  • Bombesin
  • Sirolimus
  • Wortmannin