Cell invasion and IL-8 production pathways initiated by YadA of Yersinia pseudotuberculosis require common signalling molecules (FAK, c-Src, Ras) and distinct cell factors.

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  • Author(s): Eitel J;Eitel J; Heise T; Thiesen U; Dersch P
  • Source:
    Cellular microbiology [Cell Microbiol] 2005 Jan; Vol. 7 (1), pp. 63-77.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Hindawi Country of Publication: India NLM ID: 100883691 Publication Model: Print Cited Medium: Print ISSN: 1462-5814 (Print) Linking ISSN: 14625814 NLM ISO Abbreviation: Cell Microbiol Subsets: MEDLINE
    • Publication Information:
      Publication: 2022- : Mumbai : Hindawi
      Original Publication: Oxford : Wiley-Blackwell, c1999-
    • Subject Terms:
      Signal Transduction*/physiology; Adhesins, Bacterial/*physiology ; Interleukin-8/*biosynthesis ; Yersinia pseudotuberculosis/*pathogenicity; Animals ; CSK Tyrosine-Protein Kinase ; Cell Line ; Focal Adhesion Kinase 1 ; Focal Adhesion Protein-Tyrosine Kinases ; Humans ; JNK Mitogen-Activated Protein Kinases/analysis ; MAP Kinase Kinase 1/metabolism ; Mice ; Mitogen-Activated Protein Kinase 3/metabolism ; Phosphorylation ; Protein-Tyrosine Kinases/genetics ; Protein-Tyrosine Kinases/physiology ; p38 Mitogen-Activated Protein Kinases/analysis ; raf Kinases/metabolism ; ras Proteins/genetics ; ras Proteins/physiology ; src-Family Kinases
    • Abstract:
      The YadA protein of Yersinia pseudotuberculosis promotes tight adhesion and invasion into mammalian cells through beta(1)-integrins. In this work, we demonstrate that YadA also triggers the production of interleukin-8 (IL-8) in host cells and we identify intracellular signal transduction mechanisms involved in YadA-initiated cell invasion and/or IL-8 synthesis. Tyrosine protein kinases, including the focal adhesion kinase (FAK) and c-Src, as well as the small GTPase Ras, were shown to play a significant role in both YadA-promoted cell processes. YadA-mediated cell contact led to autophosphorylation of FAK at position Tyr397 and induced GTP-loading of Ras. Furthermore, IL-8 production and invasion induced by YadA were strongly reduced in FAK- and c-Src-deficient cells and in cells overexpressing dominant interfering forms of FAK, c-Src or Ras. We also demonstrate that YadA activates the Ras-dependent Raf-MEK1/2-ERK1/2 pathway and mitogen-activated protein kinases (MAPKs) p38 and JNK. Moreover, inhibition of ERK1/2 by pharmacological agents or overexpression of dominant negative FAK, c-Src or Ras abrogated IL-8 release, whereas invasion remained unaffected. In contrast, actin polymerization and phosphatidylinositol 3-kinase (PI3K) activity is essential for YadA-promoted cell entry, but not for cytokine secretion. We conclude that YadA triggers FAK-Src complex formation and subsequent Ras activation, which leads to the stimulation of MAPKs-dependent IL-8 production or to PI3K-dependent invasion.
    • Accession Number:
      0 (Adhesins, Bacterial)
      0 (Interleukin-8)
      0 (YadA protein, Yersinia)
      EC 2.7.10.1 (Protein-Tyrosine Kinases)
      EC 2.7.10.2 (CSK Tyrosine-Protein Kinase)
      EC 2.7.10.2 (Focal Adhesion Kinase 1)
      EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
      EC 2.7.10.2 (PTK2 protein, human)
      EC 2.7.10.2 (Ptk2 protein, mouse)
      EC 2.7.10.2 (src-Family Kinases)
      EC 2.7.10.23 (CSK protein, human)
      EC 2.7.11.1 (raf Kinases)
      EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
      EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
      EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
      EC 2.7.12.2 (MAP Kinase Kinase 1)
      EC 3.6.5.2 (ras Proteins)
    • Publication Date:
      Date Created: 20041225 Date Completed: 20050711 Latest Revision: 20191210
    • Publication Date:
      20240829
    • Accession Number:
      10.1111/j.1462-5822.2004.00434.x
    • Accession Number:
      15617524