Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response.
Infection with the human microbial pathogen Helicobacter pylori is assumed to lead to invasive gastric cancer. We find that H. pylori activates the hepatocyte growth factor/scatter factor receptor c-Met, which is involved in invasive growth of tumor cells. The H. pylori effector protein CagA intracellularly targets the c-Met receptor and promotes cellular processes leading to a forceful motogenic response. CagA could represent a bacterial adaptor protein that associates with phospholipase Cgamma but not Grb2-associated binder 1 or growth factor receptor-bound protein 2. The H. pylori-induced motogenic response is suppressed and blocked by the inhibition of PLCgamma and of MAPK, respectively. Thus, upon translocation, CagA modulates cellular functions by deregulating c-Met receptor signaling. The activation of the motogenic response in H. pylori-infected epithelial cells suggests that CagA could be involved in tumor progression.
Churin
Yuri
Y
Institute of Experimental Internal Medicine, Medical Faculty, Otto-von-Guericke-University, Leipziger Strasse 44, 39120 Magdeburg, Germany.
Al-Ghoul
Laila
L
Kepp
Oliver
O
Meyer
Thomas F
TF
Birchmeier
Walter
W
Naumann
Michael
M
D048868:Adaptor Proteins, Signal Transducing; D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051380:GRB2 Adaptor Protein; D016481:Helicobacter Infections / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D016480:Helicobacter pylori / Q000378:metabolism* / Q000472:pathogenicity; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; C098587:GAB1 protein, human; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D010750:Phosphoproteins; D011506:Proteins; C080866:cagA protein, Helicobacter pylori; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D019950:Mitogen-Activated Protein Kinase 1; D010738:Type C Phospholipases; D051966:Phospholipase C gamma