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Título:
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Role of cortactin and the adaptor proteins NCK and CRK in pedestal formation by entherpathogenic "Escherichia coli" enteropatógena (EPEC).
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Autores:
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Nieto Pelegrín, Elvira
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Tipo de documento:
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texto impreso
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Editorial:
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Universidad Complutense de Madrid, 2013-01-17
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Dimensiones:
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application/pdf
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Nota general:
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info:eu-repo/semantics/openAccess
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Idiomas:
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Palabras clave:
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Estado = No publicado
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Materia = Ciencias Biomédicas: Farmacia: Microbiología
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Tipo = Tesis
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Resumen:
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The adherence of enteropathogenic Escherichia coli (EPEC) to human intestinal cells triggers the formation of actin-rich pedestals. This process requires the translocation of the bacterial translocated intimin receptor (Tir) into host cells through a type III secretion system. The insertion of Tir into the plasma membrane and its tyrosine-phosphorylation leads to the recruitment of the host cell adaptor Nck, following Tir interaction with its ligand -the EPEC intimin surface protein. Nck in turn activates the neural Wiskott-Aldrich syndrome protein (N-WASP) initiating actin polymerisation mediated by the actin-related (Arp)2/3 complex. Interestingly, the host cortactin protein activates the Arp2/3 complex and N-WASP promoting actin polymerisation by two different mechanisms. Here, we interrogate a suggested role for cortactin in Tir-mediated actin nucleation events and reveal a critical role. We propose that cortactin binds Tir through its N-terminal part in a phosphorylation independent manner. On the other hand, the SH3 domain binding and activation of N-WASP is regulated by tyrosine and serine mediated phosphorylation of cortactin. Moreover, Tir-cortactin interaction promotes Arp2/3 complex-mediated actin polymerisation in vitro. Therefore, cortactin could act on Tir:Nck:N-WASP signalling pathway and control a possible cycling activity of N-WASP underlying pedestal formation. We also demonstrate that Crk family adaptor proteins have a redundant inhibitory role in regulating actin polymerisation in actin pedestals. Furthermore, we have investigated the mechanism of the observed reduced amounts of Tir in infected Nck deficient mouse embryonic fibroblast (MEFs).
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En línea:
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https://eprints.ucm.es/id/eprint/21027/1/T34431.pdf
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