Epidermal Growth Factor Potentiates Cholecystokinin/Gastrin Receptor-mediated Ca2+ Release by Activation of Mitogen-activated Protein Kinases

Barbara Olszewska-Pazdrak, Kirk L. Ives, Jeseong Park, Courtney Townsend, Mark Hellmich

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Small differences in amplitude, duration, and temporal patterns of change in the concentration of free intracellular Ca2+ ([Ca 2+]i) can profoundly affect cell physiology, altering programs of gene expression, cell proliferation, secretory activity, and cell survival. We report a novel mechanism for amplitude modulation of [Ca 2+]i that involves mitogen-activated protein kinase (MAPK). We show that epidermal growth factor (EGF) potentiates gastrin-(1-17) (G17)-stimulated Ca2+ release from intracellular Ca2+ stores through a MAPK-dependent pathway. G17 activation of the cholecystokinin/gastrin receptor (CCK2R), a G protein-coupled receptor, stimulates release of Ca2+ from inositol 1,4,5-triphosphate-sensitive Ca2+ stores. Pretreating rat intestinal epithelial cells expressing CCK2R with EGF increased the level of G17-stimulated Ca2+ release from intracellular stores. The stimulatory effect of EGF on CCK2R-mediated Ca2+ release requires activation of the MAPK kinase (MEK)1,2/extracellular signal-regulated kinase (ERK)1,2 pathway. Inhibition of the MEK1,2/ERK1,2 pathway by either serum starvation or treatment with selective MEK1,2 inhibitors PD98059 and U0126 or expression of a dominant-negative mutant form of MEK1 decreased the amplitude of the G17-stimulated Ca2+ release response. Activation of the MEK1,2/ERK1,2 pathway either by pretreating cells with EGF or by expression of constitutively active K-ras (K-rasV12G) or MEK1 (MEK1*) increased the amplitude of G17-stimulated Ca2+ release. Although EGF, MEK1*, and K-rasV12G activated the MEK1,2/ERK1,2 pathway, they did not increase [Ca2+]i in the absence of G17. These data demonstrate that the activation state of the MEK1,2/ERK1,2 pathway can modulate the amplitude of the CCK2R-mediated Ca2+ release response and identify a novel mechanism for cross-talk between EGF receptor- and CCK 2R-regulated signaling pathways.

Original languageEnglish (US)
Pages (from-to)1853-1860
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number3
DOIs
StatePublished - Jan 16 2004

Fingerprint

Cholecystokinin B Receptor
Cholecystokinin Receptors
Cholecystokinin
Mitogen-Activated Protein Kinases
Epidermal Growth Factor
Chemical activation
Gastrins
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase Kinases
MAP Kinase Kinase 1
Cell Physiological Phenomena
Inositol 1,4,5-Trisphosphate
Mitogen-Activated Protein Kinase 3
Amplitude modulation
Mitogen-Activated Protein Kinase 1
Physiology
Cell proliferation
G-Protein-Coupled Receptors
Starvation
Epidermal Growth Factor Receptor

ASJC Scopus subject areas

  • Biochemistry

Cite this

Epidermal Growth Factor Potentiates Cholecystokinin/Gastrin Receptor-mediated Ca2+ Release by Activation of Mitogen-activated Protein Kinases. / Olszewska-Pazdrak, Barbara; Ives, Kirk L.; Park, Jeseong; Townsend, Courtney; Hellmich, Mark.

In: Journal of Biological Chemistry, Vol. 279, No. 3, 16.01.2004, p. 1853-1860.

Research output: Contribution to journalArticle

@article{7b4966ab007246fdaafe1aca8dd4f8e1,
title = "Epidermal Growth Factor Potentiates Cholecystokinin/Gastrin Receptor-mediated Ca2+ Release by Activation of Mitogen-activated Protein Kinases",
abstract = "Small differences in amplitude, duration, and temporal patterns of change in the concentration of free intracellular Ca2+ ([Ca 2+]i) can profoundly affect cell physiology, altering programs of gene expression, cell proliferation, secretory activity, and cell survival. We report a novel mechanism for amplitude modulation of [Ca 2+]i that involves mitogen-activated protein kinase (MAPK). We show that epidermal growth factor (EGF) potentiates gastrin-(1-17) (G17)-stimulated Ca2+ release from intracellular Ca2+ stores through a MAPK-dependent pathway. G17 activation of the cholecystokinin/gastrin receptor (CCK2R), a G protein-coupled receptor, stimulates release of Ca2+ from inositol 1,4,5-triphosphate-sensitive Ca2+ stores. Pretreating rat intestinal epithelial cells expressing CCK2R with EGF increased the level of G17-stimulated Ca2+ release from intracellular stores. The stimulatory effect of EGF on CCK2R-mediated Ca2+ release requires activation of the MAPK kinase (MEK)1,2/extracellular signal-regulated kinase (ERK)1,2 pathway. Inhibition of the MEK1,2/ERK1,2 pathway by either serum starvation or treatment with selective MEK1,2 inhibitors PD98059 and U0126 or expression of a dominant-negative mutant form of MEK1 decreased the amplitude of the G17-stimulated Ca2+ release response. Activation of the MEK1,2/ERK1,2 pathway either by pretreating cells with EGF or by expression of constitutively active K-ras (K-rasV12G) or MEK1 (MEK1*) increased the amplitude of G17-stimulated Ca2+ release. Although EGF, MEK1*, and K-rasV12G activated the MEK1,2/ERK1,2 pathway, they did not increase [Ca2+]i in the absence of G17. These data demonstrate that the activation state of the MEK1,2/ERK1,2 pathway can modulate the amplitude of the CCK2R-mediated Ca2+ release response and identify a novel mechanism for cross-talk between EGF receptor- and CCK 2R-regulated signaling pathways.",
author = "Barbara Olszewska-Pazdrak and Ives, {Kirk L.} and Jeseong Park and Courtney Townsend and Mark Hellmich",
year = "2004",
month = "1",
day = "16",
doi = "10.1074/jbc.M309481200",
language = "English (US)",
volume = "279",
pages = "1853--1860",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "3",

}

TY - JOUR

T1 - Epidermal Growth Factor Potentiates Cholecystokinin/Gastrin Receptor-mediated Ca2+ Release by Activation of Mitogen-activated Protein Kinases

AU - Olszewska-Pazdrak, Barbara

AU - Ives, Kirk L.

AU - Park, Jeseong

AU - Townsend, Courtney

AU - Hellmich, Mark

PY - 2004/1/16

Y1 - 2004/1/16

N2 - Small differences in amplitude, duration, and temporal patterns of change in the concentration of free intracellular Ca2+ ([Ca 2+]i) can profoundly affect cell physiology, altering programs of gene expression, cell proliferation, secretory activity, and cell survival. We report a novel mechanism for amplitude modulation of [Ca 2+]i that involves mitogen-activated protein kinase (MAPK). We show that epidermal growth factor (EGF) potentiates gastrin-(1-17) (G17)-stimulated Ca2+ release from intracellular Ca2+ stores through a MAPK-dependent pathway. G17 activation of the cholecystokinin/gastrin receptor (CCK2R), a G protein-coupled receptor, stimulates release of Ca2+ from inositol 1,4,5-triphosphate-sensitive Ca2+ stores. Pretreating rat intestinal epithelial cells expressing CCK2R with EGF increased the level of G17-stimulated Ca2+ release from intracellular stores. The stimulatory effect of EGF on CCK2R-mediated Ca2+ release requires activation of the MAPK kinase (MEK)1,2/extracellular signal-regulated kinase (ERK)1,2 pathway. Inhibition of the MEK1,2/ERK1,2 pathway by either serum starvation or treatment with selective MEK1,2 inhibitors PD98059 and U0126 or expression of a dominant-negative mutant form of MEK1 decreased the amplitude of the G17-stimulated Ca2+ release response. Activation of the MEK1,2/ERK1,2 pathway either by pretreating cells with EGF or by expression of constitutively active K-ras (K-rasV12G) or MEK1 (MEK1*) increased the amplitude of G17-stimulated Ca2+ release. Although EGF, MEK1*, and K-rasV12G activated the MEK1,2/ERK1,2 pathway, they did not increase [Ca2+]i in the absence of G17. These data demonstrate that the activation state of the MEK1,2/ERK1,2 pathway can modulate the amplitude of the CCK2R-mediated Ca2+ release response and identify a novel mechanism for cross-talk between EGF receptor- and CCK 2R-regulated signaling pathways.

AB - Small differences in amplitude, duration, and temporal patterns of change in the concentration of free intracellular Ca2+ ([Ca 2+]i) can profoundly affect cell physiology, altering programs of gene expression, cell proliferation, secretory activity, and cell survival. We report a novel mechanism for amplitude modulation of [Ca 2+]i that involves mitogen-activated protein kinase (MAPK). We show that epidermal growth factor (EGF) potentiates gastrin-(1-17) (G17)-stimulated Ca2+ release from intracellular Ca2+ stores through a MAPK-dependent pathway. G17 activation of the cholecystokinin/gastrin receptor (CCK2R), a G protein-coupled receptor, stimulates release of Ca2+ from inositol 1,4,5-triphosphate-sensitive Ca2+ stores. Pretreating rat intestinal epithelial cells expressing CCK2R with EGF increased the level of G17-stimulated Ca2+ release from intracellular stores. The stimulatory effect of EGF on CCK2R-mediated Ca2+ release requires activation of the MAPK kinase (MEK)1,2/extracellular signal-regulated kinase (ERK)1,2 pathway. Inhibition of the MEK1,2/ERK1,2 pathway by either serum starvation or treatment with selective MEK1,2 inhibitors PD98059 and U0126 or expression of a dominant-negative mutant form of MEK1 decreased the amplitude of the G17-stimulated Ca2+ release response. Activation of the MEK1,2/ERK1,2 pathway either by pretreating cells with EGF or by expression of constitutively active K-ras (K-rasV12G) or MEK1 (MEK1*) increased the amplitude of G17-stimulated Ca2+ release. Although EGF, MEK1*, and K-rasV12G activated the MEK1,2/ERK1,2 pathway, they did not increase [Ca2+]i in the absence of G17. These data demonstrate that the activation state of the MEK1,2/ERK1,2 pathway can modulate the amplitude of the CCK2R-mediated Ca2+ release response and identify a novel mechanism for cross-talk between EGF receptor- and CCK 2R-regulated signaling pathways.

UR - http://www.scopus.com/inward/record.url?scp=0345826108&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0345826108&partnerID=8YFLogxK

U2 - 10.1074/jbc.M309481200

DO - 10.1074/jbc.M309481200

M3 - Article

C2 - 14602717

AN - SCOPUS:0345826108

VL - 279

SP - 1853

EP - 1860

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 3

ER -