H. pylori-controlled c-Abl activity as a regulator of cell migration and apoptosis  

Infections with the class-I carcinogen Helicobacter pylori (H. pylori) is associated with the indcution and progression of chronic gastritis, ulceration, mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancer. While MALT lymphoma can be treated by antibiotics as the first line therapy, the prognosis of gastric cancer is still poor and represents one of the leading causes for cancer-related deaths worldwide. H. pylori stimulates a drastic motogenic response in infected gastric epithelial host cells, which is enhanced by translocation of the pathogenic factor and oncoprotein cytotoxin associated gene A (CagA) into host cells via a specialized type IV secretion system (T4SS). Once injected into the cytosol CagA is rapidly tyrosine phosphorylated by Src family kinases followed by Src inactivation. Hence, it remained unknown why CagA is constantly phosphorylated in sustained H. pylori infections to induce cell migration, while other substrates of Src kinases are dephosphorylated. In our studies, we identified the non-receptor tyrosine kinase c-Abl as a crucial mediator of H. pylori-induced migration and novel CagA kinase in epithelial cells.


                                                                         from: Posselt et al., 2019, Cell Commun Signal

The role of c-Abl in CagA-dependent pathways is well established; however, the knowledge of CagA-independent c-Abl processes is scarce. We investigated the activity and subcellular localization of c-Abl in vitro and in vivo and unraveled a novel mechanism of c-Abl in CagA-dependent and -independent pathways leading to gastric H. pylori pathogenesis. We identified strong c-Abl threonine 735 phosphorylation (pAbl T735) mediated by the T4SS effector D-glycero-β-D-manno-heptose-1,7-bisphosphate (βHBP) and protein kinase C (PKC) as a new c-Abl kinase. pAbl T735 interacts with 14–3-3 proteins, which causes cytoplasmic retention of c-Abl, where it potentiates H. pylori-mediated cell elongation and migration. Further, the nuclear exclusion of pAbl T735 attenuates caspase-8 and caspase-9-dependent apoptosis. Importantly, in human patients suffering from H. pylori-mediated gastritis, c-Abl expression and pAbl T735 phosphorylation are drastically enhanced as compared to type C gastritis patients or healthy individuals. This is a novel regulatory mechanism in H. pylori-infected gastric epithelial cells by which H. pylori determines the subcellular localization of activated c-Abl to control H. pylori-mediated EMT-like processes while decreasing cell death.

Important publications:

  • Posselt et al., 2019, Cell Commun Signal
  • Müller et al., 2012, J Clin Invest
  • Poppe et al., 2007, Oncogene
  • News
    The Austrian Academy of Sciences has awarded Mag. Dr. Daniel Ehrmann, university assistant and doctoral candidate in the Department of German Studies, four year APART-Grant, which he will start on the1. 3. 2021.During this time he will complete his post doctoral thesis project „Aggregation. Relationaliity and the Constellations of Literature (1650 – 1950). Toward a medium range historical model.
    On the 05th March 2021 Univ. Prof. John W. C. Dunlop is holding a lecture on the topic of zum "Swarming Behaviour in Confinement - How curved surfaces influence pattern formation in biology." The lecture will take place at 14:00/ 2 pm online via Webex. The Department of Biological Sciences cordially invites you to attend.
    The project funding programme for research between PLUS and South East Asian partner universities, ASEA-UNINET Call 2021-2022 (Project implementation period: 1st October 2021 - 30th September 2022) is now open.
    Prof. Dr. Jude Lal Fernando, Assistant Professor at the Irish School of Ecumenics at Trinity College Dublin, will be holding lectures in SS 2021 on the topic of "Interreligious Relations in Asia" at the Centre for Intercultural Theology in the area of Religious Studies.
    The Project Application BioMat-TEM with the total volume of €1,948 million within the Framework of the Infrastructure funding from the Austrian Research Promotion Agenvy (FFG) has been approved.
    Six researchers from Europe and the USA were recently honored with the prestigious IFIP TC13 Pioneer Award for outstanding contributions on the topic of Human-Computer Interaction worldwide.Among them is the Head of HCI at the PLUS, Prof. Manfred Tscheligi.
    The programme for the summer semester is now online and the courses will be released shortly. We have improved our entrepreneurship courses. Register by the 14th March 2021.
    The Centre for Intercultural Theology and the Study of Religions and the University of Fribourg are organising an interdisciplinary online conference from the 16th-17th April 2021 (Start 16th April 2021 at 14:15).
    The restrictions of the pandemic – not only at the university – are becoming even more testing. Thank to everyone who, despite all the difficulties, has helped to keep the university running as best they can.
  • Veranstaltungen
  • 04.03.21 Grenzgänge - Folgen von neuen Grenzen für Arbeit und Unternehmen 4.3.2021
    05.03.21 Swarming Behaviour in Confinement How curved surfaces influence pattern formation in biology.
    09.03.21 Storytelling in der alltäglichen und beruflichen Kommunikation
  • Alumni Club
  • University of Salzburg's facebook site University of Salzburg's twitter site University of Salzburg's instagram site University of Salzburg's flickr site University of Salzburg's vimeo site