Proteomics

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Phosphoproteomics of cAMP signaling of adenylate cyclase toxin in mouse dendritic cells


ABSTRACT: The whooping cough agent, Bordetella pertussis, subverts dendritic cell (DCs) functions through powerful immunomodulatory activities of its toxins. Here we focused on the signaling action of the adenylate cyclase toxin (CyaA) that targets myeloid cells expressing the αMβ2 integrin CD11b/CD18 (known as complement receptor 3 (CR3) or Mac-1). CyaA delivers an extremely catalytically potent adenylyl cyclase enzyme domain into the cytosol of phagocytes and disrupts their innate and adaptive immune functions through unregulated production of the key signaling molecule cAMP. Here we describe the global phosphoproteomic analysis of cAMP signaling in murine bone marrow-derived DCs exposed to CyaA. Gathered data reveal toxin-triggered alternations of phosphorylation status of proteins regulating actin cytoskeleton, chromatin remodeling, mTOR activity and IL-10 gene expression. The reported findings highlight the complexity of subversive physiological manipulation that is exerted on myeloid phagocytes by the cAMP-generating adenylate cyclase toxin of Bordetellae.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Primary Cell, Dendritic Cell, Cell Culture, Bone Marrow

DISEASE(S): Pertussis

SUBMITTER: Ivo Fabrik  

LAB HEAD: Peter Šebo

PROVIDER: PXD004733 | Pride | 2017-11-29

REPOSITORIES: Pride

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Phosphoproteomics of cAMP signaling of Bordetella adenylate cyclase toxin in mouse dendritic cells.

Novák Jakub J   Fabrik Ivo I   Linhartová Irena I   Link Marek M   Černý Ondřej O   Stulík Jiří J   Šebo Peter P  

Scientific reports 20171124 1


The adenylate cyclase toxin (CyaA) of the whooping cough agent Bordetella pertussis subverts immune functions of host myeloid cells expressing the α<sub>M</sub>β<sub>2</sub> integrin (CD11b/CD18, CR3 or Mac-1). CyaA delivers into cytosol of cells an extremely catalytically active adenylyl cyclase enzyme, which disrupts the innate and adaptive immune functions of phagocytes through unregulated production of the key signaling molecule cAMP. We have used phosphoproteomics to analyze cAMP signaling  ...[more]

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