Helicobacter pylori CagA phosphorylation status determines the gp130-activated SHP2/ERK and JAK/STAT signal transduction pathways in gastric epithelial cells

Ohk Lee, Jie Hyun Kim, Yeun Jung Choi, Michael H. Pillinger, Seok Yong Kim, Martin J. Blaser, Yong Chan Lee

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

The Helicobacter pylori protein CagA may undergo tyrosine phosphorylation following its entry into human gastric epithelial cells with downstream effects on signal transduction. Disruption of the gp130 receptor that modulates the balance of the SHP2/ERK and JAK/STAT pathways enhanced peptic ulceration and gastric cancer in gp130 knock-out mice. In this study, we evaluated the effect of translocated CagA in relation to its tyrosine phosphorylation status on the gp130-mediated signal switch between the SHP2/ERK and JAK/STAT3 pathways. We showed that in the presence of CagA, SHP2 was recruited to gp130. Phosphorylated CagA showed enhanced SHP2 binding activity and ERK1/2 phosphorylation, whereas unphosphorylated CagA showed preferential STAT3 activation. These findings indicate that the phosphorylation status of CagA affects the signal switch between the SHP2/ERK and JAK/STAT3 pathways through gp130, providing a novel mechanism to explain H. pylori signaling.

Original languageEnglish
Pages (from-to)16042-16050
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number21
DOIs
Publication statusPublished - 2010 May 21

Fingerprint

Signal transduction
Phosphorylation
Helicobacter pylori
Signal Transduction
Stomach
Epithelial Cells
Tyrosine
Switches
Knockout Mice
Stomach Neoplasms
Digestion
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

@article{2820c4262bae4a99a703b935c0fa2dc2,
title = "Helicobacter pylori CagA phosphorylation status determines the gp130-activated SHP2/ERK and JAK/STAT signal transduction pathways in gastric epithelial cells",
abstract = "The Helicobacter pylori protein CagA may undergo tyrosine phosphorylation following its entry into human gastric epithelial cells with downstream effects on signal transduction. Disruption of the gp130 receptor that modulates the balance of the SHP2/ERK and JAK/STAT pathways enhanced peptic ulceration and gastric cancer in gp130 knock-out mice. In this study, we evaluated the effect of translocated CagA in relation to its tyrosine phosphorylation status on the gp130-mediated signal switch between the SHP2/ERK and JAK/STAT3 pathways. We showed that in the presence of CagA, SHP2 was recruited to gp130. Phosphorylated CagA showed enhanced SHP2 binding activity and ERK1/2 phosphorylation, whereas unphosphorylated CagA showed preferential STAT3 activation. These findings indicate that the phosphorylation status of CagA affects the signal switch between the SHP2/ERK and JAK/STAT3 pathways through gp130, providing a novel mechanism to explain H. pylori signaling.",
author = "Ohk Lee and Kim, {Jie Hyun} and Choi, {Yeun Jung} and Pillinger, {Michael H.} and Kim, {Seok Yong} and Blaser, {Martin J.} and Lee, {Yong Chan}",
year = "2010",
month = "5",
day = "21",
doi = "10.1074/jbc.M110.111054",
language = "English",
volume = "285",
pages = "16042--16050",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "21",

}

Helicobacter pylori CagA phosphorylation status determines the gp130-activated SHP2/ERK and JAK/STAT signal transduction pathways in gastric epithelial cells. / Lee, Ohk; Kim, Jie Hyun; Choi, Yeun Jung; Pillinger, Michael H.; Kim, Seok Yong; Blaser, Martin J.; Lee, Yong Chan.

In: Journal of Biological Chemistry, Vol. 285, No. 21, 21.05.2010, p. 16042-16050.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Helicobacter pylori CagA phosphorylation status determines the gp130-activated SHP2/ERK and JAK/STAT signal transduction pathways in gastric epithelial cells

AU - Lee, Ohk

AU - Kim, Jie Hyun

AU - Choi, Yeun Jung

AU - Pillinger, Michael H.

AU - Kim, Seok Yong

AU - Blaser, Martin J.

AU - Lee, Yong Chan

PY - 2010/5/21

Y1 - 2010/5/21

N2 - The Helicobacter pylori protein CagA may undergo tyrosine phosphorylation following its entry into human gastric epithelial cells with downstream effects on signal transduction. Disruption of the gp130 receptor that modulates the balance of the SHP2/ERK and JAK/STAT pathways enhanced peptic ulceration and gastric cancer in gp130 knock-out mice. In this study, we evaluated the effect of translocated CagA in relation to its tyrosine phosphorylation status on the gp130-mediated signal switch between the SHP2/ERK and JAK/STAT3 pathways. We showed that in the presence of CagA, SHP2 was recruited to gp130. Phosphorylated CagA showed enhanced SHP2 binding activity and ERK1/2 phosphorylation, whereas unphosphorylated CagA showed preferential STAT3 activation. These findings indicate that the phosphorylation status of CagA affects the signal switch between the SHP2/ERK and JAK/STAT3 pathways through gp130, providing a novel mechanism to explain H. pylori signaling.

AB - The Helicobacter pylori protein CagA may undergo tyrosine phosphorylation following its entry into human gastric epithelial cells with downstream effects on signal transduction. Disruption of the gp130 receptor that modulates the balance of the SHP2/ERK and JAK/STAT pathways enhanced peptic ulceration and gastric cancer in gp130 knock-out mice. In this study, we evaluated the effect of translocated CagA in relation to its tyrosine phosphorylation status on the gp130-mediated signal switch between the SHP2/ERK and JAK/STAT3 pathways. We showed that in the presence of CagA, SHP2 was recruited to gp130. Phosphorylated CagA showed enhanced SHP2 binding activity and ERK1/2 phosphorylation, whereas unphosphorylated CagA showed preferential STAT3 activation. These findings indicate that the phosphorylation status of CagA affects the signal switch between the SHP2/ERK and JAK/STAT3 pathways through gp130, providing a novel mechanism to explain H. pylori signaling.

UR - http://www.scopus.com/inward/record.url?scp=77952410241&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952410241&partnerID=8YFLogxK

U2 - 10.1074/jbc.M110.111054

DO - 10.1074/jbc.M110.111054

M3 - Article

C2 - 20348091

AN - SCOPUS:77952410241

VL - 285

SP - 16042

EP - 16050

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 21

ER -