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p110α hot spot muta...
p110α hot spot mutations E545K and H1047R exert metabolic reprogramming independently of p110α kinase activity
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- Chaudhari, Aditi (author)
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden
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- Krumlinde, Daniel (author)
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden
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- Lundqvist, Annika (author)
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden
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- Akyürek, Levent M. (author)
- Department of Medical Chemistry and Cell biology, University of Gothenburg, Sweden
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- Bandaru, Sashidhar (author)
- Department of Medical Chemistry and Cell biology, University of Gothenburg, Sweden
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- Skålén, Kristina (author)
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden
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- Ståhlman, Marcus (author)
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden
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- Borén, Jan (author)
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden
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- Wettergren, Yvonne (author)
- Department of Surgery, University of Gothenburg, Sweden
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- Ejeskär, Katarina, 1969- (author)
- Högskolan i Skövde,Institutionen för biovetenskap,Forskningscentrum för Systembiologi,Department of Medical and Clinical Genetics, University of Gothenburg, Sweden,Tumörbiologi, Tumor Biology
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- Rotter Sopasakis, Victoria (author)
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
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(creator_code:org_t)
- American Society for Microbiology, 2015
- 2015
- English.
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In: Molecular and Cellular Biology. - : American Society for Microbiology. - 0270-7306 .- 1098-5549. ; 35:19, s. 3258-3273
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- The phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit p110α is the most frequently mutated kinase in human cancer, and the hot spot mutations E542K, E545K, and H1047R are the most common mutations in p110α. Very little is known about the metabolic consequences of the hot spot mutations of p110α in vivo. In this study, we used adenoviral gene transfer in mice to investigate the effects of the E545K and H1047R mutations on hepatic and whole-body glucose metabolism. We show that hepatic expression of these hot spot mutations results in rapid hepatic steatosis, paradoxically accompanied by increased glucose tolerance, and marked glycogen accumulation. In contrast, wild-type p110α expression does not lead to hepatic accumulation of lipids or glycogen despite similar degrees of upregulated glycolysis and expression of lipogenic genes. The reprogrammed metabolism of the E545K and H1047R p110α mutants was surprisingly not dependent on altered p110α lipid kinase activity.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (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)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Medical sciences
- Medicin
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- art (subject category)
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Chaudhari, Aditi
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Krumlinde, Danie ...
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Lundqvist, Annik ...
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Akyürek, Levent ...
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Bandaru, Sashidh ...
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Skålén, Kristina
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Ståhlman, Marcus
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Borén, Jan
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Wettergren, Yvon ...
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Ejeskär, Katarin ...
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Rotter Sopasakis ...
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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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and Medical Genetics
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
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NATURAL SCIENCES
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Molecular and Ce ...
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University of Skövde