SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes. / Henriksson, Emma; Säll, Johanna; Gormand, Amélie; Wasserstrom, Sebastian; Morrice, Nicholas A; Fritzen, Andreas Mæchel; Foretz, Marc; Campbell, David G; Sakamoto, Kei; Ekelund, Mikael; Degerman, Eva; Stenkula, Karin G; Göransson, Olga.

In: Journal of Cell Science, Vol. 128, No. 3, 2015, p. 472-486.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Henriksson, E, Säll, J, Gormand, A, Wasserstrom, S, Morrice, NA, Fritzen, AM, Foretz, M, Campbell, DG, Sakamoto, K, Ekelund, M, Degerman, E, Stenkula, KG & Göransson, O 2015, 'SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes', Journal of Cell Science, vol. 128, no. 3, pp. 472-486. https://doi.org/10.1242/jcs.153932

APA

Henriksson, E., Säll, J., Gormand, A., Wasserstrom, S., Morrice, N. A., Fritzen, A. M., Foretz, M., Campbell, D. G., Sakamoto, K., Ekelund, M., Degerman, E., Stenkula, K. G., & Göransson, O. (2015). SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes. Journal of Cell Science, 128(3), 472-486. https://doi.org/10.1242/jcs.153932

Vancouver

Henriksson E, Säll J, Gormand A, Wasserstrom S, Morrice NA, Fritzen AM et al. SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes. Journal of Cell Science. 2015;128(3):472-486. https://doi.org/10.1242/jcs.153932

Author

Henriksson, Emma ; Säll, Johanna ; Gormand, Amélie ; Wasserstrom, Sebastian ; Morrice, Nicholas A ; Fritzen, Andreas Mæchel ; Foretz, Marc ; Campbell, David G ; Sakamoto, Kei ; Ekelund, Mikael ; Degerman, Eva ; Stenkula, Karin G ; Göransson, Olga. / SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes. In: Journal of Cell Science. 2015 ; Vol. 128, No. 3. pp. 472-486.

Bibtex

@article{148c222eff0b4a6ba59bb5a64f4dbd69,
title = "SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes",
abstract = "Salt-inducible kinase 2 (SIK2) is an 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-phosphorylation of SIK2 on Ser358. Modulation of SIK2 in adipocytes resulted in altered phosphorylation of CREB-regulated transcription co-activator 2 (CRTC2) and -3, 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 protein levels, whereas cells treated with CRTC2 or HDAC4 siRNA displayed increased GLUT4. Over-expression 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 cAMP/PKA reduces the interaction of SIK2 with CRTCs and PP2A. Downstream, SIK2 promotes GLUT4 levels and glucose uptake in adipocytes.",
author = "Emma Henriksson and Johanna S{\"a}ll and Am{\'e}lie Gormand and Sebastian Wasserstrom and Morrice, {Nicholas A} and Fritzen, {Andreas M{\ae}chel} and Marc Foretz and Campbell, {David G} and Kei Sakamoto and Mikael Ekelund and Eva Degerman and Stenkula, {Karin G} and Olga G{\"o}ransson",
note = "CURIS 2015 NEXS 053",
year = "2015",
doi = "10.1242/jcs.153932",
language = "English",
volume = "128",
pages = "472--486",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "The/Company of Biologists Ltd.",
number = "3",

}

RIS

TY - JOUR

T1 - SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes

AU - Henriksson, Emma

AU - Säll, Johanna

AU - Gormand, Amélie

AU - Wasserstrom, Sebastian

AU - Morrice, Nicholas A

AU - Fritzen, Andreas Mæchel

AU - Foretz, Marc

AU - Campbell, David G

AU - Sakamoto, Kei

AU - Ekelund, Mikael

AU - Degerman, Eva

AU - Stenkula, Karin G

AU - Göransson, Olga

N1 - CURIS 2015 NEXS 053

PY - 2015

Y1 - 2015

N2 - Salt-inducible kinase 2 (SIK2) is an 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-phosphorylation of SIK2 on Ser358. Modulation of SIK2 in adipocytes resulted in altered phosphorylation of CREB-regulated transcription co-activator 2 (CRTC2) and -3, 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 protein levels, whereas cells treated with CRTC2 or HDAC4 siRNA displayed increased GLUT4. Over-expression 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 cAMP/PKA reduces the interaction of SIK2 with CRTCs and PP2A. Downstream, SIK2 promotes GLUT4 levels and glucose uptake in adipocytes.

AB - Salt-inducible kinase 2 (SIK2) is an 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-phosphorylation of SIK2 on Ser358. Modulation of SIK2 in adipocytes resulted in altered phosphorylation of CREB-regulated transcription co-activator 2 (CRTC2) and -3, 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 protein levels, whereas cells treated with CRTC2 or HDAC4 siRNA displayed increased GLUT4. Over-expression 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 cAMP/PKA reduces the interaction of SIK2 with CRTCs and PP2A. Downstream, SIK2 promotes GLUT4 levels and glucose uptake in adipocytes.

U2 - 10.1242/jcs.153932

DO - 10.1242/jcs.153932

M3 - Journal article

C2 - 25472719

VL - 128

SP - 472

EP - 486

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 3

ER -

ID: 129784513