Cholecystokinin stimulates heat shock protein 27 phosphorylation in rat pancreas both in vivo and in vitro

Gastroenterology. 1997 Apr;112(4):1354-61. doi: 10.1016/s0016-5085(97)70149-5.


Background & aims: Mammalian heat shock protein 27 (hsp27) is believed to function under normal physiological conditions and during cellular stress. Recent studies indicate a role for hsp27 in regulating actin-cytoskeletal dynamics. In the present study, secretagogue-regulated phosphorylation of hsp27 in rat exocrine pancreas was investigated both in vivo and in isolated acinar cells.

Methods: Western analysis after two-dimensional electrophoresis was used to measure the phosphorylation of hsp27 after treatment of rats or acinar cells with secretagogues. Cholecystokinin-stimulated mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 activity was measured after immunoprecipitation of the kinase.

Results: hsp27 exists as three isoforms in acini: one nonphosphorylated (pI 6.2) and two phosphorylated (pIs 5.9 and 5.7) forms. Infusion of rats with a secretory or supermaximal dose of cerulein produced an acidic shift in hsp27, indicating an increase in its phosphorylation; the higher dose, known to cause pancreatitis, had a twofold greater effect. In isolated acini, increases in hsp27 phosphorylation were evident at 10 pmol/L and maximal at 1 nmol/L cholecystokinin. The hsp27-specific kinase MAPKAP kinase 2 was activated 2.4-fold with 1 nmol/L cholecystokinin treatment.

Conclusions: hsp27 phosphorylation was stimulated by low and high concentrations of cholecystokinin, both in vivo and in vitro. Phosphorylation was potentially mediated via the MAPKAP kinase 2 intracellular signaling pathway.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • Cholecystokinin / pharmacology*
  • Enzyme Activation
  • Heat-Shock Proteins / metabolism*
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Pancreas / cytology
  • Pancreas / metabolism*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • Rats
  • Rats, Sprague-Dawley


  • Heat-Shock Proteins
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Cholecystokinin
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases