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Abl tyrosine kinases are required for infection by Shigella flexneri.

Publication ,  Journal Article
Burton, EA; Plattner, R; Pendergast, AM
Published in: EMBO J
October 15, 2003

Infection by the opportunistic bacterial pathogen Shigella flexneri stimulates tyrosine phosphorylation of host cell proteins, but the kinases involved and their effects on the regulation of cell signaling pathways during bacterial entry remain largely undefined. Here, we demonstrate a requirement for the Abl family of tyrosine kinases during Shigella internalization. Family members Abl and Arg are catalytically activated upon Shigella infection, accumulate at the site of bacterial entry, and are required for efficient bacterial uptake, as internalization is blocked upon targeted deletion of these kinases or treatment with a specific pharmacological inhibitor. We identify the adapter protein Crk as a target for Abl kinases during Shigella uptake, and show that a phosphorylation-deficient Crk mutant significantly inhibits bacterial uptake. Moreover, we define a novel signaling pathway activated during Shigella entry that links Abl kinase phosphorylation of Crk to activation of the Rho family GTPases Rac and Cdc42. Together, these findings reveal a new role for the Abl kinases, and suggest a novel approach to treatment of Shigella infections through inhibition of host cell signaling pathways.

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Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

October 15, 2003

Volume

22

Issue

20

Start / End Page

5471 / 5479

Location

England

Related Subject Headings

  • Signal Transduction
  • Shigella flexneri
  • Proto-Oncogene Proteins c-abl
  • Mice, Knockout
  • Mice
  • Humans
  • Hela Cells
  • HeLa Cells
  • Developmental Biology
  • Cells, Cultured
 

Citation

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Burton, E. A., Plattner, R., & Pendergast, A. M. (2003). Abl tyrosine kinases are required for infection by Shigella flexneri. EMBO J, 22(20), 5471–5479. https://doi.org/10.1093/emboj/cdg512
Burton, Elizabeth A., Rina Plattner, and Ann Marie Pendergast. “Abl tyrosine kinases are required for infection by Shigella flexneri.EMBO J 22, no. 20 (October 15, 2003): 5471–79. https://doi.org/10.1093/emboj/cdg512.
Burton EA, Plattner R, Pendergast AM. Abl tyrosine kinases are required for infection by Shigella flexneri. EMBO J. 2003 Oct 15;22(20):5471–9.
Burton, Elizabeth A., et al. “Abl tyrosine kinases are required for infection by Shigella flexneri.EMBO J, vol. 22, no. 20, Oct. 2003, pp. 5471–79. Pubmed, doi:10.1093/emboj/cdg512.
Burton EA, Plattner R, Pendergast AM. Abl tyrosine kinases are required for infection by Shigella flexneri. EMBO J. 2003 Oct 15;22(20):5471–5479.

Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

October 15, 2003

Volume

22

Issue

20

Start / End Page

5471 / 5479

Location

England

Related Subject Headings

  • Signal Transduction
  • Shigella flexneri
  • Proto-Oncogene Proteins c-abl
  • Mice, Knockout
  • Mice
  • Humans
  • Hela Cells
  • HeLa Cells
  • Developmental Biology
  • Cells, Cultured