Sökning: WFRF:(Juhasz Peter)
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Quantitative proteo...
Quantitative proteomic analysis of fibroblast nuclear proteins after stimulation with mitogen activated protein kinase inhibiting heparan sulfate
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- Malmström, Johan (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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Marchese, Jason (författare)
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Juhasz, Peter (författare)
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- Pukac, Laurel (författare)
- Harvard Medical School
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- Karnovsky, Morris (författare)
- Harvard Medical School
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- Marko-Varga, György (författare)
- Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Westergren-Thorsson, Gunilla (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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(creator_code:org_t)
- Elsevier BV, 2005
- 2005
- Engelska 10 s.
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Ingår i: Journal of Chromatography. B. - : Elsevier BV. - 1873-376X .- 1570-0232. ; 815:1-2, s. 333-342
- Relaterad länk:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Certain structures of heparan sulfate (HS) inhibit cell proliferation of fibroblasts. Whether this inhibition is dependent on inhibition of mitogenic signaling pathways or nuclear translocation of HS is unknown. In this study we investigated possible mechanism(s) and structural requirements by which antiproliferative glycosaminoglycans exert their effects on mitogen-activated protein kinase (MAP kinase) phosphorylation, a key intermediate in cell signaling, followed by quantitative proteomic analysis of nuclear proteins by stable isotope coded affinity tags, multidimensional chromatography and tandem mass spectrometry. Serum starved human lung fibroblasts were stimulated with serum, platelet derived growth factor (PDGF-BB) or epidermal growth factor (EGF) in the presence of structurally different glycosaminoglycans. Antiproliferative heparan sulfate with a high content of 2-O-sulfated iduronic acid (IdoA-2SO4) and heavily sulfated glucosamine, and the structurally related glycosaminoglycan heparin inhibited significantly serum stimulated MAP kinase phosphorylation, by at least 80% when stimulated by serum and HS6. We hypothesized that the inhibition of the MAP kinase pathway will have effect in the nuclear proteome. Therefore an isotope coded affinity tag (ICAT) reagent labeling of nuclear proteins and tandem mass spectrometry was applied, resulting in the identification and quantification of 206 proteins. Several nuclear proteins were found to be induced or repressed due to HS stimulation, where the repression EBNA-2 co-activator and the induction of PML protein were of special interest. These results show that heparan sulfate with high content of (IdoA-2SO4) and heavily sulfated glucosamine specifically inhibits MAP kinase activation with a subsequent change in the nuclear proteome of the fibroblast.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Binding Sites
- Cell Proliferation
- Cells, Cultured
- Down-Regulation
- Fibroblasts
- Glycosaminoglycans
- Heparitin Sulfate
- Humans
- Isotope Labeling
- Lung
- Mass Spectrometry
- Mitogen-Activated Protein Kinases
- Nuclear Proteins
- Phosphorylation
- Journal Article
- Research Support, Non-U.S. Gov't
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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