Invasion of human epithelial cells by Pseudomonas aeruginosa involves src-like tyrosine kinases p60Src and p59Fyn.
Pseudomonas aeruginosa plays a major role in respiratory tract infections or sepsis in patients with cystic fibrosis or upon suppression of the immune system. Several P. aeruginosa strains have been shown to be internalized by human epithelial cells; however, the molecular mechanisms of the invasion process are poorly characterized. Here, we show that the internalization of P. aeruginosa into human epithelial cells results in and requires activation of the Src-like tyrosine kinases p59Fyn and p60Src and the consequent tyrosine phosphorylation of several eukaryotic proteins. The significance of Src-like tyrosine kinase activation is shown by an almost complete blockade of P. aeruginosa internalization, but not adhesion, upon inhibition of Src-like tyrosine kinases. Likewise, inhibition of P. aeruginosa binding to CFTR, which has been shown to block P. aeruginosa internalization, prevents Src and Fyn activation, supporting a pivotal role of Src-like tyrosine kinases for invasion by P. aeruginosa.
Esen
M
M
Department of Physiology, University of Tuebingen, 72076 Tuebingen, Germany.
Grassmé
H
H
Riethmüller
J
J
Riehle
A
A
Fassbender
K
K
Gulbins
E
E
D002478:Cells, Cultured; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051076:Proto-Oncogene Proteins c-fyn; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*
C505032:CFTR protein, human; D011518:Proto-Oncogene Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D016392:Proto-Oncogene Proteins pp60(c-src)