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Mitogen-Activated P...
Mitogen-Activated Protein Kinase Signaling Regulates Proteoglycan Composition of Mast Cell Secretory Granules
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- Frisk, Jun Mei Hu (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Uppsala University
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- Kjellén, Lena (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Uppsala University
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- Melo, Fabio R. (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Uppsala University
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- Öhrvik, Helena (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Uppsala University
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- Pejler, Gunnar (författare)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB)
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(creator_code:org_t)
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- 2018-07-19
- 2018
- Engelska.
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 9
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://www.frontier...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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https://res.slu.se/i...
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Abstract
Ämnesord
Stäng
- Mast cells (MCs) are characterized by an abundance of lysosome-like secretory granules filled with immunomodulatory compounds including histamine, cytokines, lysosomal hydrolases, MC-restricted proteases, and serglycin proteoglycans. The latter are essential for promoting the storage of other granule compounds and are built up of the serglycin core protein to which highly sulfated and thereby negatively charged glycosaminoglycan (GAG) side chains of heparin or chondroitin sulfate type are attached. In the search for mechanisms operating in regulating MC granule homeostasis, we here investigated the role of mitogen-activated protein kinase (MAPK) signaling. We show that inhibition of MEK1/2 (a MAPK kinase) leads to increased metachromatic staining of MC granules, indicative of increased proteoglycan content. Indeed, MEK1/2 inhibition caused a profound increase in the expression of the gene coding for the serglycin core protein and of genes coding for various enzymes involved in the biosynthesis/sulfation of the GAGs attached to the serglycin core protein. This was accompanied by corresponding increases in the levels of the respective GAGs. Deletion of the serglycin core protein abrogated the induction of enzymes operative in proteoglycan synthesis, indicating that availability of the serglycin proteoglycan core protein has a regulatory function impacting on the expression of the various serglycin-modifying enzymes. MEK1/2 inhibition also caused a substantial increase in the expression of granule-localized, proteoglycan-binding proteases. Altogether, this study identifies a novel role for MAPK signaling in regulating the content of secretory granules in MCs.
Ämnesord
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- 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
- mast cells
- mitogen-activated protein kinase
- MEK1/2
- proteoglycans
- heparin
- chondroitin sulfate
- tryptase
- serglycin
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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