The Helicobacter pylori virulence factor CagA promotes Erk1/2-mediated Bad phosphorylation in lymphocytes: a mechanism of CagA-inhibited lymphocyte apoptosis.
The Helicobacter pylori virulence factor, CagA, is causally linked to lymphoma of gastric mucosa-associated lymphoid tissue (MALT). However, it is unclear how CagA promotes the development of gastric MALT lymphoma. We investigated whether CagA modulates the activation of Erk1/2 and their downstream apoptosis regulators in B lymphocytes. Transfection of B1 lymphocytes with cagA transiently increased Erk1/2 phosphorylation, which was negatively regulated by MKP-1 and MKP-6. Activation of Erk1/2 led to phosphorylation of Bad at Ser-112, as confirmed with a chemical Erk1/2 inhibitor. However, CagA-induced Erk1/2 activation did not alter expression of either Bcl-2 or Bax. Importantly, cagA-transfected B1 cells were significantly protected against apoptosis induced by hydroxyurea. Our results reveal that CagA, to some extent like IL-3, can enhance lymphocytes' ability to evade apoptosis through phosphorylation of Bad. This may account, at least in part, for the ability of CagA to promote lymphomagenesis.
Zhu
Yongliang
Y
Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. zhuyongliangch@yahoo.com.cn
Wang
Caihua
C
Huang
Jian
J
Ge
Zhen
Z
Dong
Qi
Q
Zhong
Xian
X
Su
Yanyan
Y
Zheng
Shu
S
D020816:Amino Acid Motifs; D000942:Antigens, Bacterial / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D047468:Immunoprecipitation; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D037521:Virulence Factors; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C080866:cagA protein, Helicobacter pylori; D048049:Extracellular Signal-Regulated MAP Kinases; D017027:Protein Tyrosine Phosphatases; D006918:Hydroxyurea