PAR1b takes the stage in the morphogenetic and motogenetic activity of Helicobacter pylori CagA oncoprotein

Yukie Yamahashi, Masanori Hatakeyama

Research output: Contribution to journalComment/debate

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)11-17
Number of pages7
JournalCell Adhesion and Migration
Volume7
Issue number1
DOIs
Publication statusPublished - 01-01-2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

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