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Interferon stimulated changes in the brain phosphoproteome

ABSTRACT: Type I interferons (IFN-Is) are immunoregulatory cytokines that are essential for normal host antiviral responses. The current understanding is that IFN-Is mediate their effects through the expression of several hundred interferon-regulated genes. Here we identified a novel IFN-I response mechanism that relies on widespread changes in protein phosphorylation. IFN-I-induced phosphorylation in primary murine microglia and astrocytes – key IFN-I-responding cells of the central nervous system – was rapid and thus largely independent of gene expression. Based on in silico analysis, this mechanism relies predominantly on a small number of kinase families. Further, functional analysis suggested that this rapid response induces an immediate reactive state in cells and prepares them for the subsequent transcriptomic response. Similar extensive phosphoproteome changes were also present in a mouse model for IFN-I-induced neuroinflammatory diseases. Strikingly, the altered phosphoproteome in these transgenic mice predicted the clinical and pathological outcome of neuroinflammatory disease. These findings demonstrate for the first time a novel mechanism by which IFN-Is mediate cellular responses.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Cell Suspension Culture, Mature Astrocyte, Cell Culture, Mature Microglial Cell

DISEASE(S): Inflammation

SUBMITTER: Melanie White

LAB HEAD: Melanie Yvonne White

PROVIDER: PXD014443 | Pride | 2021-11-02

REPOSITORIES: Pride

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			Action	DRS
	160809_QE+_MYW_Hofer_Mono_Fr-(2).pride.mgf.gz	Mgf
	160809_QE+_MYW_Hofer_Mono_Fr.pride.mgf.gz	Mgf
	160809_QE+_MYW_Hofer_Mono_Fr.pride.mztab.gz	Mztab
	160809_QE+_MYW_Hofer_NonPhos_Fr-(2.2.0.388).pride.mgf.gz	Mgf
	160809_QE+_MYW_Hofer_NonPhos_Fr.pride.mgf.gz	Mgf

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