Role of tyrosine kinases and the tyrosine phosphatase SptP in the interaction of Salmonella with host cells.
Salmonella has evolved an intimate functional interface with its host. Central to this interface is a battery of bacterial proteins delivered into host cells via a specialized organelle termed the type III secretion system. A subset of these bacterial proteins stimulates cellular responses by activating the Rho family GTPases Cdc42 and Rac. Stimulation of these responses leads to actin cytoskeleton reorganization and the activation of cellular transcription factors that result in bacterial uptake and proinflammatory cytokine production. Remarkably, the cellular responses stimulated by Salmonella are quickly reversed by another bacterial protein, SptP, which exerts its function as a GTPase-activating protein (GAP) for Cdc42 and Rac. In addition to its GAP activity located within its amino-terminus, the carboxy-terminal domain of SptP possesses potent tyrosine phosphatase activity. We show here that the tyrosine phosphatase activity of SptP is involved in reversing the MAP kinase activation that results from Salmonella infection. We also demonstrate an important role for tyrosine kinases, including ACK, in the cellular responses induced by Salmonella. We also found that a potential target for the tyrosine phosphatase activity of SptP is the intermediate filament protein vimentin, which is recruited to the membrane ruffles stimulated by Salmonella.
Murli
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Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale School of Medicine, New Haven, CT 06536, USA.
Watson
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Galán
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JE
D000199:Actins / Q000378:metabolism; D001426:Bacterial Proteins; D002467:Cell Nucleus / Q000378:metabolism; D003599:Cytoskeleton / Q000502:physiology; D016209:Interleukin-8 / Q000096:biosynthesis; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism* / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism* / Q000502:physiology; D012475:Salmonella; D012486:Salmonella typhimurium / Q000201:enzymology* / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D001426:Bacterial Proteins; D016209:Interleukin-8; D014746:Vimentin; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D017027:Protein Tyrosine Phosphatases; C439890:sptP protein, Salmonella typhimurium; D020764:cdc42 GTP-Binding Protein