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© Pierre Gounon
Entrée de Listeria dans une cellule épithéliale (Grossissement X 10000). Image colorisée.
Publication : FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Salmonella enteritidis Rck-mediated invasion requires activation of Rac1, which is dependent on the class I PI 3-kinases-Akt signaling pathway

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in FASEB journal : official publication of the Federation of American Societies for Experimental Biology - 30 Dec 2011

Mijouin L, Rosselin M, Bottreau E, Pizarro-Cerda J, Cossart P, Velge P, Wiedemann A

Link to Pubmed [PMID] – 22210834

FASEB J. 2012 Apr;26(4):1569-81

The Salmonella outer membrane protein Rck mediates a Zipper-like entry mechanism controlled by Rac, the Arp2/3 complex, and actin polymerization. However, little is known about the early steps leading to Rac activation and Rck-mediated internalization. The use of pharmacological inhibitors or PI 3-kinase dominant-negative mutant induced more than 80% less invasion without affecting attachment. Moreover, Rck-mediated internalization caused an increase in the association of p85 with at least one tyrosine-phosphorylated protein, indicating that class I PI 3-kinase activity was stimulated. We also report that this PI 3-kinase activity is essential for Rac1 activation. However, Rac recruitment at the Rck-mediated entry site was independent of its activation. Using a pharmacological approach or Akt-knockout cells, we also demonstrated that Akt was phosphorylated in response to Rck-mediated internalization as demonstrated by immunoblotting analysis and that all three Akt isoforms were required during this process. Overall, our results describe a signaling pathway involving tyrosine phosphorylation, class I PI 3-kinase, Akt activation, and Rac activation, leading to Rck-dependent Zipper entry. The specificity of this signaling pathway with regard to that of the type 3 secretion system, which is the other invasion process of Salmonella, is discussed.