Structural and functional diversity in the PAR1b/MARK2-binding region of Helicobacter pylori CagA

摘要: Helicobacter pylori (H. pylori) cagA-positive strains are associated with gastritis, peptic ulcerations, and gastric adenocarcinoma. Upon delivery into epithelial cells, the cagA-encoded CagA protein specifically binds aberrantly activates SHP-2 oncoprotein in a manner that is dependent on tyrosine phosphorylation. CagA-deregulated then elicits aberrant Erk activation while causing an elongated cell shape known as hummingbird phenotype. In polarized also to PAR1b/MARK2 inhibits PAR1b kinase activity, thereby disrupting tight junctions polarity independent of We show here CagA-multimerization (CM) sequence mediates interaction not only essential for CagA-triggered junctional defects but plays important role induction phenotype by potentiating CagA-SHP-2 complex formation. CM isolated from East Asian H. (referred E-CM sequence) more strongly than Western W-CM sequence). Within species, ability bind proportional number sequences. Furthermore, level PAR1b-binding activity correlates magnitude degree induction. Our findings reveal structural diversity determinant virulence CagA, bacterial carcinogenesis. (Cancer Sci 2008; 99: 2004–2011)