Abstract:
:Dysregulation of signaling pathways in multiple sclerosis (MS) can be analyzed by phosphoproteomics in peripheral blood mononuclear cells (PBMCs). We performed in vitro kinetic assays on PBMCs in 195 MS patients and 60 matched controls and quantified the phosphorylation of 17 kinases using xMAP assays. Phosphoprotein levels were tested for association with genetic susceptibility by typing 112 single-nucleotide polymorphisms (SNPs) associated with MS susceptibility. We found increased phosphorylation of MP2K1 in MS patients relative to the controls. Moreover, we identified one SNP located in the PHDGH gene and another on IRF8 gene that were associated with MP2K1 phosphorylation levels, providing a first clue on how this MS risk gene may act. The analyses in patients treated with disease-modifying drugs identified the phosphorylation of each receptor's downstream kinases. Finally, using flow cytometry, we detected in MS patients increased STAT1, STAT3, TF65, and HSPB1 phosphorylation in CD19+ cells. These findings indicate the activation of cell survival and proliferation (MAPK), and proinflammatory (STAT) pathways in the immune cells of MS patients, primarily in B cells. The changes in the activation of these kinases suggest that these pathways may represent therapeutic targets for modulation by kinase inhibitors.
journal_name
Proc Natl Acad Sci U S Aauthors
Kotelnikova E,Kiani NA,Messinis D,Pertsovskaya I,Pliaka V,Bernardo-Faura M,Rinas M,Vila G,Zubizarreta I,Pulido-Valdeolivas I,Sakellaropoulos T,Faigle W,Silberberg G,Masso M,Stridh P,Behrens J,Olsson T,Martin R,Paul Fdoi
10.1073/pnas.1818347116subject
Has Abstractpub_date
2019-05-07 00:00:00pages
9671-9676issue
19eissn
0027-8424issn
1091-6490pii
1818347116journal_volume
116pub_type
杂志文章abstract::Deuterium Fourier-transform nuclear magnetic resonance spectra have been obtained of 1-myristoyl 2-(14,14,14-trideutero)myristoyl phosphatidylcholine bilayers at 34.1 MHz by using the quadrupole echo pulse technique. Thereby, we have investigated the effects upon the deuterated dimyristoyl phosphatidylcholine bilayers...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.75.10.4657
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.1802354115
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1980-04-01 00:00:00