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SIK2 regulates CRTC...
SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes
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- Henriksson, Emma (author)
- Lund University,Lunds universitet,Proteinfosforylering,Forskargrupper vid Lunds universitet,Protein Phosphorylation,Lund University Research Groups
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- Säll, Johanna (author)
- Lund University,Lunds universitet,Proteinfosforylering,Forskargrupper vid Lunds universitet,Protein Phosphorylation,Lund University Research Groups
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- Gormand, Amelie (author)
- Lund University,Lunds universitet,Proteinfosforylering,Forskargrupper vid Lunds universitet,Protein Phosphorylation,Lund University Research Groups
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- Wasserstrom, Sebastian (author)
- Lund University,Lunds universitet,Glukostransport och proteintrafficking,Forskargrupper vid Lunds universitet,Glucose Transport and Protein Trafficking,Lund University Research Groups
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Morrice, Nicholas A. (author)
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Fritzen, Andreas M. (author)
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Foretz, Marc (author)
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Campbell, David G. (author)
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Sakamoto, Kei (author)
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- Ekelund, Mikael (author)
- Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Degerman, Eva (author)
- Lund University,Lunds universitet,Signaltransduktionsforskning,Forskargrupper vid Lunds universitet,Insulin Signal Transduction,Lund University Research Groups
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- Stenkula, Karin (author)
- Lund University,Lunds universitet,Glukostransport och proteintrafficking,Forskargrupper vid Lunds universitet,Glucose Transport and Protein Trafficking,Lund University Research Groups
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- Göransson, Olga (author)
- Lund University,Lunds universitet,Proteinfosforylering,Forskargrupper vid Lunds universitet,Signaltransduktionsforskning,Protein Phosphorylation,Lund University Research Groups,Insulin Signal Transduction
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(creator_code:org_t)
- 2014-01-01
- 2015
- English.
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In: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 128:3, s. 472-486
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Abstract
Subject headings
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- Salt-inducible kinase 2 (SIK2) is an AMP-activated protein kinase (AMPK) related kinase abundantly expressed in adipose tissue. Our aim was to identify molecular targets and functions of SIK2 in adipocytes, and to address the role of PKA-mediated phosphorylation of SIK2 on Ser358. Modulation of SIK2 in adipocytes resulted in altered phosphorylation of CREB-regulated transcription co-activator 2 (CRTC2), CRTC3 and class IIa histone deacetylase 4 (HDAC4). Furthermore, CRTC2, CRTC3, HDAC4 and protein phosphatase 2A (PP2A) interacted with SIK2, and the binding of CRTCs and PP2A to wild-type but not Ser358Ala SIK2, was reduced by cAMP elevation. Silencing of SIK2 resulted in reduced GLUT4 (also known as SLC2A4) protein levels, whereas cells treated with CRTC2 or HDAC4 siRNA displayed increased levels of GLUT4. Overexpression or pharmacological inhibition of SIK2 resulted in increased and decreased glucose uptake, respectively. We also describe a SIK2-CRTC2-HDAC4 pathway and its regulation in human adipocytes, strengthening the physiological relevance of our findings. Collectively, we demonstrate that SIK2 acts directly on CRTC2, CRTC3 and HDAC4, and that the cAMP-PKA pathway reduces the interaction of SIK2 with CRTCs and PP2A. Downstream, SIK2 increases GLUT4 levels and glucose uptake in adipocytes.
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
- SIK2
- Adipocyte
- CRTC2
- CRTC3
- HDAC4
- PP2A
- Glucose uptake
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Henriksson, Emma
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Säll, Johanna
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Gormand, Amelie
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Wasserstrom, Seb ...
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Morrice, Nichola ...
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Fritzen, Andreas ...
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show more...
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Foretz, Marc
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Campbell, David ...
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Sakamoto, Kei
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Ekelund, Mikael
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Degerman, Eva
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Stenkula, Karin
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Göransson, Olga
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show less...
- About the subject
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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 Cell and Molecul ...
- Articles in the publication
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Journal of Cell ...
- By the university
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Lund University