Grb2 is a key mediator of helicobacter pylori CagA protein activities.
CagA delivered from Helicobacter pylori into gastric epithelial cells undergoes tyrosine phosphorylation and induces host cell morphological changes. Here we show that CagA can interact with Grb2 both in vitro and in vivo, which results in the activation of the Ras/MEK/ERK pathway and leads to cell scattering as well as proliferation. Importantly, this ability of CagA is independent from the tyrosine phosphorylation, which occurs within the five repeated EPIYA sequences (PY region) of CagA. However, the PY region appears to be indispensable for the Grb2 binding and induction of the cellular responses. Thus, intracellular CagA via its binding to Grb2 may act as a transducer for stimulating growth factor-like downstream signals which lead to cell morphological changes and proliferation, the causes of H. pylori-induced gastric hyperplasia.
Mimuro
Hitomi
H
Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Suzuki
Toshihiko
T
Tanaka
Jiro
J
Asahi
Momoyo
M
Haas
Rainer
R
Sasakawa
Chihiro
C
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D048429:Cell Size; D051380:GRB2 Adaptor Protein; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D011506:Proteins; C080866:cagA protein, Helicobacter pylori; D019000:Phosphotyrosine