title: Src-dependent tyrosine phosphorylation of non-muscle myosin heavy chain-IIA restricts Listeria monocytogenes cellular infection.
abstract: Bacterial pathogens often interfere with host tyrosine phosphorylation cascades to control host responses and cause infection. Given the role of tyrosine phosphorylation events in different human infections and our previous results showing the activation of the tyrosine kinase Src upon incubation of cells with Listeria monocytogenes, we searched for novel host proteins undergoing tyrosine phosphorylation upon L. monocytogenes infection. We identify the heavy chain of the non-muscle myosin IIA (NMHC-IIA) as being phosphorylated in a specific tyrosine residue in response to L. monocytogenes infection. We characterize this novel post-translational modification event and show that, upon L. monocytogenes infection, Src phosphorylates NMHC-IIA in a previously uncharacterized tyrosine residue (Tyr-158) located in its motor domain near the ATP-binding site. In addition, we found that other intracellular and extracellular bacterial pathogens trigger NMHC-IIA tyrosine phosphorylation. We demonstrate that NMHC-IIA limits intracellular levels of L. monocytogenes, and this is dependent on the phosphorylation of Tyr-158. Our data suggest a novel mechanism of regulation of NMHC-IIA activity relying on the phosphorylation of Tyr-158 by Src.
authors: From the Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal, the Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal, the Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal.
authors: Maria Teresa
authors: MT
authors: Almeida
authors: From the Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal, the Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal, the Medical Research Council, Centre for Molecular Bacteriology and Infection, Imperial College, London, London SW7 2AZ, United Kingdom.
authors: Francisco S
authors: FS
authors: Mesquita
authors: From the Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal, the Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal, the Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal.
authors: Rui
authors: R
authors: Cruz
authors: From the Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal, the Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal, and.
authors: Hugo
authors: H
authors: Osório
authors: From the Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal, the Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal.
authors: Rafael
authors: R
authors: Custódio
authors: From the Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal, the Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal, the Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal.
authors: Cláudia
authors: C
authors: Brito
authors: the Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655.
authors: Didier
authors: D
authors: Vingadassalom
authors: From the Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal, the Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal.
authors: Mariana
authors: M
authors: Martins
authors: the Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655.
authors: John M
authors: JM
authors: Leong
authors: the Medical Research Council, Centre for Molecular Bacteriology and Infection, Imperial College, London, London SW7 2AZ, United Kingdom.
authors: David W
authors: DW
authors: Holden
authors: From the Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal, the Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal, didier@ibmc.up.pt.
authors: Didier
authors: D
authors: Cabanes
authors: From the Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal, the Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal, srsousa@ibmc.up.pt.
authors: Sandra
authors: S
authors: Sousa
mesh_terms: D000595:Amino Acid Sequence; D058491:Bacterial Load; D018938:Caco-2 Cells; D004789:Enzyme Activation; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008089:Listeria monocytogenes / Q000502:physiology*; D008088:Listeriosis / Q000201:enzymology* / Q000382:microbiology; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D019061:src-Family Kinases; D024507:Nonmuscle Myosin Type IIA
keywords: Cellular Infection; Gram-positive Bacteria; Host-Pathogen Interaction; Intracellular Bacterial Pathogen; Listeria monocytogenes; Myosin; Non-muscle Myosin IIA; Phosphotyrosine Signaling; Post-translational Modification; Src
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