gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Helicobacter pylori controls serine and tyrosine phosphorylation of cortactin to induce actin cytoskeletal rearrangements and host cell scattering

Meeting Abstract

  • corresponding author presenting/speaker Ruth Wittelsberger - Institut für Medizinische Mikrobiologie, Universitätsklinikum, Magdeburg, Deutschland
  • Frank Meyer - Klinik für Chirurgie, Universitätsklinikum, Magdeburg
  • Sabine Brandt - Institut für Medizinische Mikrobiologie, Universitätsklinikum, Magdeburg
  • Nicole Tegtmeyer - Institut für Medizinische Mikrobiologie, Universitätsklinikum, Magdeburg
  • Wolfgang König - Institut für Medizinische Mikrobiologie, Universitätsklinikum, Magdeburg
  • Steffen Backert - Institut für Medizinische Mikrobiologie, Universitätsklinikum, Magdeburg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO201

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dkk2006/06dkk311.shtml

Veröffentlicht: 20. März 2006

© 2006 Wittelsberger et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Cortactin is an actin-binding protein and central regulator of the actin cytoskeleton. In vitro, cortactin binds and activates N-WASP via its SH3 domain to stimulate actin polymerization by the Arp2/3 complex. Cortactin is a target for phosphorylation by Src family tyrosine kinases and by serine/threonine kinases that include Erk1/2, however, the mechanism by which cortactin phosphorylation events modulate the architecture of the actin cytoskeleton in vivo is unknown. Interestingly, the gene encoding cortactin is amplified in some human cancers and cortactin is suspected to play a major role in tumour invasion. In addition, cortactin is also a common target exploited by microbes during infection. We have used the class 1 carcinogen Helicobacter pylori as a model system to study the role and function of cortactin during infection of gastric epithelial cells. H. pylori translocates the CagA effector protein into the host cell cytoplasm and induces both the activation of Erk and the inactivation of Src signaling. This induces the redistribution of cortactin to actin-rich cellular protrusions and global rearrangements of the host cell actin cytoskeleton leading to cell scattering. Activation of Erk and subsequent serine phosphorylation of full-length cortactin strongly increased its ability to bind to and stimulate N-WASP-mediated actin polymerization and cell scattering in vivo. By contrast, tyrosine phosphorylation strongly reduced the latter activity and even suppressed serine-phosphorylated cortactin. Thus, Src phosphorylation terminates cortactin activation of N-WASP and blocks cell scattering. These findings support an in vivo model where Erk or Src phosphorylation of cortactin acts as a molecular switch modulating its ability to bind and activate N-WASP-dependent actin polymerization. Taken together, CagA specifically triggers the activation of cortactin by two independent pathways, the stimulation of Erk and inactivation of Src. This has an important impact on how H. pylori abuses cortactin to control the architecture of the host actin cytoskeleton and cell scattering which may contribute to the development of gastric cancer.