CAS/Crk signalling mediates uptake of Yersinia into human epithelial cells.
Uptake of Yersinia pseudotuberculosis into mammalian cells involves engagement of beta1 integrin receptors by the bacterial protein invasin. This triggers a host response that involves tyrosine phosphorylation of proteins and the induction of actin rearrangements that lead to cellular uptake of bacteria. In this report, we show that the focal adhesion protein CAS plays an important role in Yersinia uptake, and that its function is linked to the phosphorylation-dependent interaction between CAS and Crk. These studies demonstrate that Yersinia binding to host cell receptors initiates a cascade of events involving tyrosine phosphorylation of CAS, subsequent formation of functional CAS-Crk complexes and the activity of the small GTP-binding protein Rac1. The delineation of this pathway lends support for a model in which Yersinia uptake into human epithelial cells is dependent upon aspects of host signalling pathways that govern actin cytoskeleton remodelling and cell migration.
Weidow
C L
CL
Department of Microbiology and Cancer Center, University of Virginia Health System, Charlottesville 22908-0734, USA.
Black
D S
DS
Bliska
J B
JB
Bouton
A H
AH
D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D022001:Focal Adhesions; D006367:HeLa Cells / Q000382:microbiology*; D006801:Humans; D015151:Immunoblotting; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D015398:Signal Transduction; D014162:Transfection; D015011:Yersinia pseudotuberculosis / Q000472:pathogenicity* / Q000502:physiology; D015012:Yersinia pseudotuberculosis Infections / Q000382:microbiology*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D001425:Bacterial Outer Membrane Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D011494:Protein Kinases; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia; D020830:rac1 GTP-Binding Protein