TY - JOUR
T1 - PAR1b takes the stage in the morphogenetic and motogenetic activity of Helicobacter pylori CagA oncoprotein
AU - Yamahashi, Yukie
AU - Hatakeyama, Masanori
N1 - Funding Information:
We thank the members of the Hatakeyama lab for useful discussions. The authors declare no competing financial interests. The works presented here were supported by Grants-in-Aid for the Scientific Research on Innovative Area from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (M.H.).
PY - 2013
Y1 - 2013
N2 - Helicobacter pylori CagA oncoprotein is critically involved in gastric carcinogenesis. Upon delivery into gastric epithelial cells via type IV secretion, CagA induces an extremely elongated cell-shape known as the hummingbird phenotype, which is associated with massive changes in actin cytoskeleton and elevated motility. With the notion that the hummingbird phenotype reflects pathogenic/oncogenic activity of CagA, many studies have focused on the mechanism through which CagA induces the morphological change. Once delivered, CagA interacts with host proteins such as oncogenic phosphatase SHP2 and polarity-regulating kinase PAR1b. Whereas the essential role of the CagA-SHP2 interaction in inducing the hummingbird phenotype has been extensively investigated, involvement of the CagA-PAR1b interaction in the morphological change has remained uncertain. Recently, we found that the CagA-PAR1b interaction, which inhibits PAR1b kinase activity, influences the actin cytoskeletal system and potentiates the magnitude of the hummingbird phenotype. We also found that PAR1b inactivates a RhoA-specific GEF, GEF-H1, via phosphorylation and thereby inhibits cortical actin and stress fiber formation. Collectively, these findings indicate that CagA-mediated inhibition of PAR1b promotes RhoA-dependent actin-cytoskeletal rearrangement and thereby strengthens the hummingbird phenotype induced by CagA-stimulated SHP2 during infection with H. pylori cagA-positive strains.
AB - Helicobacter pylori CagA oncoprotein is critically involved in gastric carcinogenesis. Upon delivery into gastric epithelial cells via type IV secretion, CagA induces an extremely elongated cell-shape known as the hummingbird phenotype, which is associated with massive changes in actin cytoskeleton and elevated motility. With the notion that the hummingbird phenotype reflects pathogenic/oncogenic activity of CagA, many studies have focused on the mechanism through which CagA induces the morphological change. Once delivered, CagA interacts with host proteins such as oncogenic phosphatase SHP2 and polarity-regulating kinase PAR1b. Whereas the essential role of the CagA-SHP2 interaction in inducing the hummingbird phenotype has been extensively investigated, involvement of the CagA-PAR1b interaction in the morphological change has remained uncertain. Recently, we found that the CagA-PAR1b interaction, which inhibits PAR1b kinase activity, influences the actin cytoskeletal system and potentiates the magnitude of the hummingbird phenotype. We also found that PAR1b inactivates a RhoA-specific GEF, GEF-H1, via phosphorylation and thereby inhibits cortical actin and stress fiber formation. Collectively, these findings indicate that CagA-mediated inhibition of PAR1b promotes RhoA-dependent actin-cytoskeletal rearrangement and thereby strengthens the hummingbird phenotype induced by CagA-stimulated SHP2 during infection with H. pylori cagA-positive strains.
KW - Actin cytoskeleton
KW - Apical-basal polarity
KW - Cell migration
KW - Front-rear polarity
KW - GEF-H1
KW - Helicobacter pylori caga
KW - PAR1/MARK
KW - RhoA
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U2 - 10.4161/cam.21936
DO - 10.4161/cam.21936
M3 - Comment/debate
C2 - 23076215
AN - SCOPUS:84872174477
SN - 1933-6918
VL - 7
SP - 11
EP - 17
JO - Cell Adhesion and Migration
JF - Cell Adhesion and Migration
IS - 1
ER -