Involvement of c-Src tyrosine kinase upstream of class I phosphatidylinositol (PI) 3-kinases in Salmonella Enteritidis Rck protein-mediated invasion.
The Salmonella outer membrane protein Rck mediates a Zipper entry mechanism controlled by tyrosine phosphorylation and class I phosphatidylinositol 3-kinase (PI 3-kinase). However, the underlying mechanism leading to this signaling cascade remains unclear. The present study showed that using Rck-coated beads or Rck-overexpressing Escherichia coli, Rck-mediated actin polymerization and invasion were blocked by PP2, a Src family tyrosine kinase inhibitor. In addition, phosphorylation of Src family kinases significantly increased after stimulation with Rck. The specific contribution of c-Src, one member of the Src family kinases, was demonstrated using c-Src-deficient fibroblasts or c-Src siRNA transfected epithelial cells. We also observed that Rck-mediated internalization led to the formation of a complex between c-Src and at least one tyrosine-phosphorylated protein. Furthermore, our results revealed that the c-Src signal molecule was upstream of PI 3-kinase during the Rck-mediated signaling pathway as Rck-mediated PI 3-kinase activation was blocked by PP2, and PI 3-kinase inhibitor had no effect on the Src phosphorylation. These results demonstrate the involvement of c-Src upstream of the PI 3-kinase in the Zipper entry process mediated by Rck.
UMR 1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique (INRA), F-37380 Nouzilly, France. Agnes.Wiedemann@tours.inra.fr
Agnès
A
Wiedemann
Manon
M
Rosselin
Lily
L
Mijouin
Elisabeth
E
Bottreau
Philippe
P
Velge
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D000081247:CSK Tyrosine-Protein Kinase; D002460:Cell Line; D004789:Enzyme Activation / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012480:Salmonella Infections / Q000235:genetics / Q000378:metabolism*; D012477:Salmonella enteritidis / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases
D001426:Bacterial Proteins; D000081247:CSK Tyrosine-Protein Kinase; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases; C000631346:CSK protein, human