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Geranylgeranyltrans...
Geranylgeranyltransferase type I (GGTase-I) deficiency hyperactivates macrophages and induces erosive arthritis in mice.
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- Khan, Omar M., 1980 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Ibrahim, Mohamed X (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Jonsson, Ing-Marie, 1949 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine
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- Karlsson, Christin, 1956 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Liu, Meng, 1976 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Sjögren, Anna-Karin, 1980 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Olofsson, Frida J, 1982 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Brisslert, Mikael, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Andersson, Sofia E M, 1979 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Ohlsson, Claes, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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- Mattsson Hultén, Lillemor, 1951 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Bokarewa, Maria, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Bergö, Martin, 1970 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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(creator_code:org_t)
- 2011
- 2011
- English.
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In: The Journal of clinical investigation. - 1558-8238. ; 121:2, s. 628-39
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https://doi.org/10.1...
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Abstract
Subject headings
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- RHO family proteins are important for the function of inflammatory cells. They are modified with a 20-carbon geranylgeranyl lipid in a process catalyzed by protein geranylgeranyltransferase type I (GGTase-I). Geranylgeranylation is viewed as essential for the membrane targeting and activity of RHO proteins. Consequently, inhibiting GGTase-I to interfere with RHO protein activity has been proposed as a strategy to treat inflammatory disorders. However, here we show that mice lacking GGTase-I in macrophages develop severe joint inflammation resembling erosive rheumatoid arthritis. The disease was initiated by the GGTase-I-deficient macrophages and was transplantable and reversible in bone marrow transplantation experiments. The cells accumulated high levels of active GTP-bound RAC1, CDC42, and RHOA, and RAC1 remained associated with the plasma membrane. Moreover, GGTase-I deficiency activated p38 and NF-κB and increased the production of proinflammatory cytokines. The results challenge the view that geranylgeranylation is essential for the activity and localization of RHO family proteins and suggest that reduced geranylgeranylation in macrophages can initiate erosive arthritis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Alkyl and Aryl Transferases
- deficiency
- genetics
- Animals
- Arthritis
- immunology
- pathology
- Cytokines
- immunology
- Macrophages
- cytology
- enzymology
- immunology
- physiology
- Mice
- Mice
- Inbred C57BL
- Mice
- Knockout
- cdc42 GTP-Binding Protein
- genetics
- metabolism
- rac1 GTP-Binding Protein
- genetics
- metabolism
- rap1 GTP-Binding Proteins
- genetics
- metabolism
- rhoA GTP-Binding Protein
- genetics
- metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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Khan, Omar M., 1 ...
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Ibrahim, Mohamed ...
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Jonsson, Ing-Mar ...
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Karlsson, Christ ...
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Liu, Meng, 1976
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Sjögren, Anna-Ka ...
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Olofsson, Frida ...
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Brisslert, Mikae ...
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Andersson, Sofia ...
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Ohlsson, Claes, ...
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Mattsson Hultén, ...
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Bokarewa, Maria, ...
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Bergö, Martin, 1 ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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The Journal of c ...
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University of Gothenburg