c-Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs

Molecular Microbiology
Markus SteinA Covacci

Abstract

The human pathogen Helicobacter pylori colonizes the mucous layer of the stomach. During parasitic infection, freely swimming bacteria adhere to the gastric epithelial cells and trigger intracellular signalling pathways. This process requires the translocation of the effector protein CagA into the host cell through a specialized type IV secretion system encoded in the cag pathogenicity island. Following transfer, CagA is phosphorylated on tyrosine residues by a host cell kinase. Here, we describe how the tyrosine phosphorylation of CagA is restricted to a previously identified repeated sequence called D1. This sequence is located in the C-terminal half of the protein and contains the five-amino-acid motif EPIYA, which is amplified by duplications in a large fraction of clinical isolates. Tyrosine phosphorylation of CagA is essential for the activation process that leads to dramatic changes in the morphology of cells growing in culture. In addition, we observed that two members of the src kinases family, c-Src and Lyn, account for most of the CagA-specific kinase activity in host cell lysates. Thus, CagA translocation followed by tyrosine phosphorylation at the EPIYA motifs promotes a growth factor-like response with intense cyt...Continue Reading

References

Dec 1, 1990·The Journal of Cell Biology·T David-Pfeuty, Y Nouvian-Dooghe
Feb 1, 1987·Experimental Cell Research·D Henderson, L Rohrschneider
Jul 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·S A CourtneidgeJ M Bishop
Mar 1, 1994·Molecular and Cellular Biology·M D SchallerJ T Parsons
Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·C T SigalM D Resh
Jun 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A CovacciN Figura
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·S CensiniA Covacci
Dec 10, 1999·Proceedings of the National Academy of Sciences of the United States of America·E D SegalL S Tompkins
Feb 3, 2000·Proceedings of the National Academy of Sciences of the United States of America·M SteinA Covacci
Feb 24, 2000·The Journal of Experimental Medicine·M AsahiC Sasakawa
Aug 2, 2000·Proceedings of the National Academy of Sciences of the United States of America·S J JurisJ E Dixon

❮ Previous
Next ❯

Citations

Oct 23, 2009·Current Microbiology·Tania Beatriz Romero-AdriánAna Antúnez
May 26, 2011·Langenbeck's Archives of Surgery·Jan Bornschein, Peter Malfertheiner
Apr 9, 2005·Trends in Microbiology·Matthias Selbach, Steffen Backert
Sep 3, 2004·Nature Reviews. Cancer·Masanori Hatakeyama
May 25, 2010·Nature Reviews. Cancer·D Brent Polk, Richard M Peek
Oct 13, 2010·Nature Reviews. Gastroenterology & Hepatology·Yoshio Yamaoka
May 17, 2007·Nature Reviews. Microbiology·Sebastian Suerbaum, Christine Josenhans
Mar 24, 2004·Nature Reviews. Microbiology·Eric Cascales, Peter J Christie
Mar 29, 2002·Molecular Microbiology·Christian BaronErich Lanka
May 13, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ludovico ButiHidde L Ploegh
Jun 24, 2009·The Journal of Biological Chemistry·Mayumi UmedaMasanori Hatakeyama
Jan 8, 2011·The Journal of Biological Chemistry·Christiane PelzRoger Vogelmann
Jul 26, 2008·Molecular Biology of the Cell·Seth R OgdenRichard M Peek
Oct 12, 2010·Clinical Microbiology Reviews·Lydia E WroblewskiKeith T Wilson
Jul 19, 2006·Clinical Microbiology Reviews·Johannes G KustersErnst J Kuipers
Oct 24, 2003·Infection and Immunity·D Scott MerrellStanley Falkow
May 23, 2003·Infection and Immunity·D Scott MerrellStanley Falkow
May 25, 2004·Infection and Immunity·Stefan MoeseSteffen Backert
Jun 22, 2006·Journal of Bacteriology·Valerie J BuslerTimothy L Cover
Jun 19, 2009·Journal of Clinical Microbiology·Dionyssios N SgourasEleftheria Roma-Giannikou
Jan 23, 2009·Journal of Clinical Microbiology·Kathleen R JonesJeong-Heon Cha

❮ Previous
Next ❯

Related Concepts

Related Feeds

CZI Human Cell Atlas Seed Network

The aim of the Human Cell Atlas (HCA) is to build reference maps of all human cells in order to enhance our understanding of health and disease. The Seed Networks for the HCA project aims to bring together collaborators with different areas of expertise in order to facilitate the development of the HCA. Find the latest research from members of the HCA Seed Networks here.

Bacterial Respiration

This feed focuses on cellular respiration in bacteria, known as bacterial respiration. Discover the latest research here.

CRISPR & Staphylococcus

CRISPR-Cas system enables the editing of genes to create or correct mutations. Staphylococci are associated with life-threatening infections in hospitals, as well as the community. Here is the latest research on how CRISPR-Cas system can be used for treatment of Staphylococcal infections.