CagA of Helicobacter pylori interacts with and inhibits the serine-threonine kinase PRK2

Jyoti Prasad Mishra, David Cohen, Andrea Zamperone, Dragana Nesic, Anne Muesch, Markus Stein

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

CagA is a multifunctional toxin of Helicobacter pylori that is secreted into host epithelial cells by a type IV secretion system. Following host cell translocation, CagA interferes with various host-cell signalling pathways. Most notably this toxin is involved in the disruption of apical-basolateral cell polarity and cell adhesion, as well as in the induction of cell proliferation, migration and cell morphological changes. These are processes that also play an important role in epithelial-to-mesenchymal transition and cancer cell invasion. In fact, CagA is considered as the only known bacterial oncoprotein. The cellular effects are triggered by a variety of CagA activities including the inhibition of serine-threonine kinase Par1b/MARK2 and the activation of tyrosine phosphatase SHP-2. Additionally, CagA was described to affect the activity of Src family kinases and C-terminal Src kinase (Csk) suggesting that interference with multiple cellular kinase- and phosphatase-associated signalling pathways is a major function of CagA. Here, we describe the effect of CagA on protein kinase C-related kinase 2 (PRK2), which acts downstream of Rho GTPases and is known to affect cytoskeletal rearrangements and cell polarity. CagA interacts with PRK2 and inhibits its kinase activity. Because PRK2 has been linked to cytoskeletal rearrangements and establishment of cell polarity, we suggest that CagA may hijack PRK2 to further manipulate cancer-related signalling pathways.

Original languageEnglish (US)
Pages (from-to)1670-1682
Number of pages13
JournalCellular Microbiology
Volume17
Issue number11
DOIs
StatePublished - Nov 1 2015

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Protein-Serine-Threonine Kinases
Helicobacter pylori
Cell Polarity
Phosphoric Monoester Hydrolases
Phosphotransferases
rho GTP-Binding Proteins
Epithelial-Mesenchymal Transition
src-Family Kinases
Oncogene Proteins
Cell Adhesion
Cell Movement
Tyrosine
Neoplasms
Epithelial Cells
Cell Proliferation
protein kinase C kinase

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

Cite this

CagA of Helicobacter pylori interacts with and inhibits the serine-threonine kinase PRK2. / Mishra, Jyoti Prasad; Cohen, David; Zamperone, Andrea; Nesic, Dragana; Muesch, Anne; Stein, Markus.

In: Cellular Microbiology, Vol. 17, No. 11, 01.11.2015, p. 1670-1682.

Research output: Contribution to journalArticle

Mishra, Jyoti Prasad ; Cohen, David ; Zamperone, Andrea ; Nesic, Dragana ; Muesch, Anne ; Stein, Markus. / CagA of Helicobacter pylori interacts with and inhibits the serine-threonine kinase PRK2. In: Cellular Microbiology. 2015 ; Vol. 17, No. 11. pp. 1670-1682.
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