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Control of cholecystokinin receptor dephosphorylation in pancreatic acinar cells.

Publication ,  Journal Article
Lutz, MP; Pinon, DI; Gates, LK; Shenolikar, S; Miller, LJ
Published in: J Biol Chem
June 5, 1993

Phosphorylation of cell surface receptors regulates the physiological response to many hormones and neurotransmitters. We have demonstrated that the receptor for cholecystokinin (CCK), the major secretagogue for the exocrine pancreas, is phosphorylated on serines in response to CCK (Klueppelberg, U.G., Gates, L.K., Gorelick, F.S., and Miller, L.J. (1991) J. Biol. Chem. 266, 2403-2408). Receptor phosphorylation was transient, even in the continued presence of agonist, and suggested a role for pancreatic protein phosphatases (PP) in regulating receptor phosphorylation in the intact cell. Treatment of acinar cells with okadaic acid increased the extent and duration of receptor phosphorylation induced by CCK. Receptor phosphorylated in the intact cell in response to CCK was used as substrate to analyze protein phosphatases in pancreatic acinar cell extracts. The predominant CCK receptor phosphatase activity was found in the cytosol and was potently inhibited by okadaic acid (IC50 = 0.2 nM). This phosphatase activity was unaffected by inhibitor-2, Ca2+, or Mg2+, suggesting that the major receptor phosphatase was PP-2A. Stimulation of cells with CCK resulted in a 3-fold increase in protein phosphatase activity toward the CCK receptor, at the same time that phosphorylase a phosphatase activity was unchanged. This increase in receptor phosphatase activity was reflected only in the cytosol, with the particulate activity unchanged. Consistent with this subcellular localization, the hormone-regulated receptor phosphatase activity was PP-2A, with chromatographic separation demonstrating activity in both PP-2A1 and PP-2A2 forms. These data suggest that CCK coordinates the activity of both protein kinases and phosphatases acting on the CCK receptor to control the extent and duration of receptor phosphorylation in the pancreatic acinar cell.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

June 5, 1993

Volume

268

Issue

16

Start / End Page

12136 / 12142

Location

United States

Related Subject Headings

  • Subcellular Fractions
  • Receptors, Cholecystokinin
  • Rats, Sprague-Dawley
  • Rats
  • Phosphorylation
  • Phosphorylase Phosphatase
  • Phosphoprotein Phosphatases
  • Pancreas
  • Okadaic Acid
  • Male
 

Citation

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Lutz, M. P., Pinon, D. I., Gates, L. K., Shenolikar, S., & Miller, L. J. (1993). Control of cholecystokinin receptor dephosphorylation in pancreatic acinar cells. J Biol Chem, 268(16), 12136–12142.
Lutz, M. P., D. I. Pinon, L. K. Gates, S. Shenolikar, and L. J. Miller. “Control of cholecystokinin receptor dephosphorylation in pancreatic acinar cells.J Biol Chem 268, no. 16 (June 5, 1993): 12136–42.
Lutz MP, Pinon DI, Gates LK, Shenolikar S, Miller LJ. Control of cholecystokinin receptor dephosphorylation in pancreatic acinar cells. J Biol Chem. 1993 Jun 5;268(16):12136–42.
Lutz, M. P., et al. “Control of cholecystokinin receptor dephosphorylation in pancreatic acinar cells.J Biol Chem, vol. 268, no. 16, June 1993, pp. 12136–42.
Lutz MP, Pinon DI, Gates LK, Shenolikar S, Miller LJ. Control of cholecystokinin receptor dephosphorylation in pancreatic acinar cells. J Biol Chem. 1993 Jun 5;268(16):12136–12142.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

June 5, 1993

Volume

268

Issue

16

Start / End Page

12136 / 12142

Location

United States

Related Subject Headings

  • Subcellular Fractions
  • Receptors, Cholecystokinin
  • Rats, Sprague-Dawley
  • Rats
  • Phosphorylation
  • Phosphorylase Phosphatase
  • Phosphoprotein Phosphatases
  • Pancreas
  • Okadaic Acid
  • Male