PMID- 25764225 OWN - NLM STAT- MEDLINE DCOM- 20160308 LR - 20211203 IS - 1615-9861 (Electronic) IS - 1615-9853 (Linking) VI - 15 IP - 12 DP - 2015 Jun TI - Phosphoproteome characterization reveals that Sendai virus infection activates mTOR signaling in human epithelial cells. PG - 2087-97 LID - 10.1002/pmic.201400586 [doi] AB - Sendai virus (SeV) is a common respiratory pathogen in mice, rats, and hamsters. Host cell recognition of SeV is mediated by pathogen recognition receptors, which recognize viral components and induce intracellular signal transduction pathways that activate the antiviral innate immune response. Viruses use host proteins to control the activities of signaling proteins and their downstream targets, and one of the most important host protein modifications regulated by viral infection is phosphorylation. In this study, we used phosphoproteomics combined with bioinformatics to get a global view of the signaling pathways activated during SeV infection in human lung epithelial cells. We identified altogether 1347 phosphoproteins, and our data shows that SeV infection induces major changes in protein phosphorylation affecting the phosphorylation of almost one thousand host proteins. Bioinformatics analysis showed that SeV infection activates known pathways including MAPK signaling, as well as signaling pathways previously not linked to SeV infection including Rho family of GTPases, HIPPO signaling, and mammalian target of rapamycin (mTOR)-signaling pathway. Further, we performed functional studies with mTOR inhibitors and siRNA approach, which revealed that mTOR signaling is needed for both the host IFN response as well as viral protein synthesis in SeV-infected human lung epithelial cells. CI - (c) 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Ohman, Tiina AU - Ohman T AD - Institute of Biotechnology, University of Helsinki, Helsinki, Finland. FAU - Soderholm, Sandra AU - Soderholm S AD - Institute of Biotechnology, University of Helsinki, Helsinki, Finland. AD - Finnish Institute of Occupational Health, Helsinki, Finland. FAU - Paidikondala, Maruthibabu AU - Paidikondala M AD - Institute of Biotechnology, University of Helsinki, Helsinki, Finland. FAU - Lietzen, Niina AU - Lietzen N AD - Institute of Biotechnology, University of Helsinki, Helsinki, Finland. FAU - Matikainen, Sampsa AU - Matikainen S AD - Finnish Institute of Occupational Health, Helsinki, Finland. FAU - Nyman, Tuula A AU - Nyman TA AD - Institute of Biotechnology, University of Helsinki, Helsinki, Finland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150427 PL - Germany TA - Proteomics JT - Proteomics JID - 101092707 RN - 0 (Phosphoproteins) RN - 0 (RNA, Messenger) RN - 9008-11-1 (Interferons) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Blotting, Western MH - Computational Biology MH - Cricetinae MH - Epithelial Cells/cytology/*metabolism MH - Humans MH - Interferons/metabolism MH - Lung Neoplasms/*metabolism/pathology/virology MH - Mice MH - Phosphoproteins/genetics/*metabolism MH - Phosphorylation MH - Protein Array Analysis MH - Proteomics/*methods MH - RNA, Messenger/genetics MH - Rats MH - Real-Time Polymerase Chain Reaction MH - Respirovirus Infections/*metabolism/virology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sendai virus/*physiology MH - Signal Transduction MH - TOR Serine-Threonine Kinases/genetics/*metabolism MH - Tumor Cells, Cultured OTO - NOTNLM OT - Bioinformatics OT - IFN response OT - Phosphoproteome OT - Virus infection OT - mTOR signaling EDAT- 2015/03/13 06:00 MHDA- 2016/03/10 06:00 CRDT- 2015/03/13 06:00 PHST- 2014/12/10 00:00 [received] PHST- 2015/02/24 00:00 [revised] PHST- 2015/03/06 00:00 [accepted] PHST- 2015/03/13 06:00 [entrez] PHST- 2015/03/13 06:00 [pubmed] PHST- 2016/03/10 06:00 [medline] AID - 10.1002/pmic.201400586 [doi] PST - ppublish SO - Proteomics. 2015 Jun;15(12):2087-97. doi: 10.1002/pmic.201400586. Epub 2015 Apr 27.