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

• Applicant: Professorin Dr. Silja Weßler
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 38787948

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-Role of c-Abl in H. pylori infection 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.

• DFG Programme: Research Grants
• International Connection: Austria