Signal transduction between enteropathogenic Escherichia coli (EPEC) and epithelial cells: EPEC induces tyrosine phosphorylation of host cell proteins to initiate cytoskeletal rearrangement and bacterial uptake.
Upon attachment to cultured HeLa cells, enteropathogenic Escherichia coli (EPEC) induces assembly of a complex cytoskeletal structure within the eucaryotic cell, localized beneath the adherent bacterium. In addition, EPEC induces its own internalization by non-phagocytic epithelial cells. We found that after binding to the epithelial cell surface, EPEC induces tyrosine phosphorylation of three eucaryotic proteins. The major phosphorylation substrate is a 90 kDa protein (Hp90). In correlation with Hp90 tyrosine phosphorylation, the EPEC-induced cytoskeletal structure also contained tyrosine phosphorylated proteins. Using tyrosine protein kinase inhibitors and EPEC mutants (cfm) that fail to induce Hp90 phosphorylation, we demonstrate that induction of Hp90 phosphorylation is involved in initiation of the cytoskeletal structure assembly and in bacterial uptake. Other non-invasive EPEC mutants (eae) are still able to induce Hp90 tyrosine phosphorylation and to initiate aggregation of the tyrosine phosphorylated proteins and some cytoskeleton components. However, eae mutants are deficient in nucleating the aggregates into an organized structure.
Rosenshine
I
I
Department of Biochemistry, University of British Columbia, Vancouver, Canada.
Donnenberg
M S
MS
Kaper
J B
JB
Finlay
B B
BB
D000470:Alkaloids / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D004848:Epithelium / Q000382:microbiology / Q000502:physiology; D004926:Escherichia coli / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D019833:Genistein; D006367:HeLa Cells; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D007700:Kinetics; D008954:Models, Biological; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D019311:Staurosporine; D014443:Tyrosine
D000470:Alkaloids; D007529:Isoflavones; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D014443:Tyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine