The carboxyl-terminal SH3 domain of the mammalian adaptor CrkII promotes internalization of Listeria monocytogenes through activation of host phosphoinositide 3-kinase.
The intracellular bacterial pathogen Listeria monocytogenes causes food-borne illnesses leading to gastroenteritis, meningitis or abortion. Listeria induces its internalization into some mammalian cells through binding of the bacterial surface protein InlB to its host receptor, the Met Receptor Tyrosine Kinase. InlB-induced activation of Met stimulates host signal transduction pathways that culminate in cell surface changes driving pathogen engulfment. One mammalian protein with the potential to couple Met to downstream signalling is the adaptor CrkII. CrkII contains an unusual carboxyl-terminal SH3 domain (SH3C) that promotes entry of Listeria. However, binding partners or downstream effectors of SH3C remain unknown. Here, we use RNA interference and overexpression studies to demonstrate that SH3C affects bacterial uptake, at least in part, through stimulation of host phosphatidylinositide (PI) 3-kinase. Experiments with latex beads coated with InlB protein indicated that one potential role of SH3C and PI 3 kinase is to promote changes in the F-actin cytoskeleton necessary for particle engulfment. Taken together, our results indicate that the CrkII SH3C domain engages a cellular ligand that regulates PI 3 kinase activity and host cell surface rearrangements.
Dokainish
Hatem
H
Department of Medical Genetics and Microbiology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Gavicherla
Balramakrishna
B
Shen
Yang
Y
Ireton
Keith
K
D000199:Actins / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D004705:Endocytosis; D004789:Enzyme Activation; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008089:Listeria monocytogenes / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D050737:Proto-Oncogene Proteins c-crk / Q000502:physiology*; D015398:Signal Transduction; D018909:src Homology Domains
D000199:Actins; D001426:Bacterial Proteins; D002867:Chromones; D008565:Membrane Proteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D050737:Proto-Oncogene Proteins c-crk; C095768:inlB protein, Listeria monocytogenes; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one