An investigation of the role of c-Abl in Helicobacter pylori infection

  • Weßler, Silja, (Projektleitung)



    Injection of the pathogenic factor CagA (cytotoxin associated gene A) of Helicobacter pylori (H. pylori) into the cytoplasm of infected epithelial cells induces drastic cell motility. Tyrosine phosphorylation of CagA by kinases of the Src family is crucial for the induction of cell migration. However, it remained unclear why CagA is constantly phosphorylated in host cells while Src kinases are inactivated. In our previous studies we have shown that the non-receptor tyrosine kinase c-Abl led to a sustained CagA phosphorylation and therefore, represents an important key molecule in H. pylori-induced cell migration. In the supposed project we aim at the investigation of the role of c-Abl in infected cells. A main focus lies on the analysis of the function of H. pylori-induced threonine 735 (Thr735) phosphorylation in c-Abl. It is hypothesized that Thr735 phosphorylation regulates the subcellular distribution of c-Abl and therefore, provides an important regulator in apoptosis and cell migration. It is planned to identify the unknown threonine kinase that phosphorylates Thr735 of c-Abl as well as the upstream signal transduction pathway. It will be further studied how Thr735 phosphorylation of c-Abl interferes with signal transduction pathways leading to apoptosis and CagA:c-Abl-mediated cell migration. The proposed project will provide information on novel c-Abl-dependent signal transduction pathways, thus provides an important insight in H. pylori-induced pathogenesis.

    1. H. pylori activates an unknown threonine kinase, which phosphorylates c-Abl: What is the identity of the threonine kinase?

    2. H. pylori-induced Thr735 phosphorylation of c-Abl is type IV secretion system (T4SS)-dependent, but CagA-independent: How is Thr735 phosphorylation of c-Abl regulated?

    3. c-Abl accumulates in H. pylori-infected cells: How is the c-Abl accumulation regulated? Is Thr735 phosphorylation necessary for accumulation? What is the function of c-Abl accumulation?

    4. c-Abl shuttles between nucleus and cytoplasm: Does H. pylori-induced Thr735 phosphorylation play a role in subcellular localization of c-Abl? Does Thr735-phosphorylated c-Abl function in H. pylori-dependent cell migration or (anti)-apoptosis?

    An investigation of the role of c-Abl in Helicobacter pylori infection
    Kurztitelregulation of c-Abl Phosphorylation
    Tatsächlicher Beginn/ -es Ende1/07/0730/06/11

    Systematik der Wissenschaftszweige 2002

    • 1410 Mikrobiologie