The AMPK-related kinase SIK2 is regulated by cAMP via phosphorylation at Ser 358 in adipocytes

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The AMPK-related kinase SIK2 is regulated by cAMP via phosphorylation at Ser 358 in adipocytes. / Henriksson, Emma; Jones, Helena A.; Patel, Kashyap; Peggie, Mark; Morrice, Nicholas; Sakamoto, Kei; Göransson, Olga.

In: Biochemical Journal, Vol. 444, No. 3, 15.06.2012, p. 503-514.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Henriksson, E, Jones, HA, Patel, K, Peggie, M, Morrice, N, Sakamoto, K & Göransson, O 2012, 'The AMPK-related kinase SIK2 is regulated by cAMP via phosphorylation at Ser 358 in adipocytes', Biochemical Journal, vol. 444, no. 3, pp. 503-514. https://doi.org/10.1042/BJ20111932

APA

Henriksson, E., Jones, H. A., Patel, K., Peggie, M., Morrice, N., Sakamoto, K., & Göransson, O. (2012). The AMPK-related kinase SIK2 is regulated by cAMP via phosphorylation at Ser 358 in adipocytes. Biochemical Journal, 444(3), 503-514. https://doi.org/10.1042/BJ20111932

Vancouver

Henriksson E, Jones HA, Patel K, Peggie M, Morrice N, Sakamoto K et al. The AMPK-related kinase SIK2 is regulated by cAMP via phosphorylation at Ser 358 in adipocytes. Biochemical Journal. 2012 Jun 15;444(3):503-514. https://doi.org/10.1042/BJ20111932

Author

Henriksson, Emma ; Jones, Helena A. ; Patel, Kashyap ; Peggie, Mark ; Morrice, Nicholas ; Sakamoto, Kei ; Göransson, Olga. / The AMPK-related kinase SIK2 is regulated by cAMP via phosphorylation at Ser 358 in adipocytes. In: Biochemical Journal. 2012 ; Vol. 444, No. 3. pp. 503-514.

Bibtex

@article{186fcd9ed0a1414791783400935bface,
title = "The AMPK-related kinase SIK2 is regulated by cAMP via phosphorylation at Ser 358 in adipocytes",
abstract = "SIK2 (salt-inducible kinase 2) is a member of the AMPK (AMP-activated protein kinase) family of kinases and is highly expressed in adipocytes. We investigated the regulation of SIK2 in adipocytes in response to cellular stimuli with relevance for adipocyte function and/or AMPK signalling. None of the treatments, including insulin, cAMP inducers or AICAR (5-amino-4- imidazolecarboxamide riboside), affected SIK2 activity towards peptide or protein substrates in vitro. However, stimulation with the cAMP-elevating agent forskolin and the β-adrenergic receptor agonist CL 316,243 resulted in a PKA (protein kinase A)-dependent phosphorylation and 14-3-3 binding of SIK2. Phosphopeptide mapping of SIK2 revealed several sites phosphorylated in response to cAMP induction, including Ser 358. Site-directed mutagenesis demonstrated that phosphorylation of Ser 358, but not the previously reported PKA site Ser 587, was required for 14-3-3 binding. Immunocytochemistry illustrated that the localization of exogenously expressed SIK2 in HEK (human embryonic kidney)-293 cells was exclusively cytosolic and remained unchanged after cAMP elevation. Fractionation of adipocytes, however, revealed a significant increase of wild-type, but not Ser358Ala, HA (haemagglutinin)-SIK2 in the cytosol and a concomitant decrease in a particulate fraction after CL 316,243 treatment. This supports a phosphorylation-dependent relocalization in adipocytes. We hypothesize that regulation of SIK2 by cAMP could play a role for the critical effects of this second messenger on lipid metabolism in adipocytes.",
keywords = "14-3-3, 3T3-l1 adipocyte, cAMP, Insulin, Phosphorylation, Salt-induced kinase (SIK)",
author = "Emma Henriksson and Jones, {Helena A.} and Kashyap Patel and Mark Peggie and Nicholas Morrice and Kei Sakamoto and Olga G{\"o}ransson",
year = "2012",
month = jun,
day = "15",
doi = "10.1042/BJ20111932",
language = "English",
volume = "444",
pages = "503--514",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "3",

}

RIS

TY - JOUR

T1 - The AMPK-related kinase SIK2 is regulated by cAMP via phosphorylation at Ser 358 in adipocytes

AU - Henriksson, Emma

AU - Jones, Helena A.

AU - Patel, Kashyap

AU - Peggie, Mark

AU - Morrice, Nicholas

AU - Sakamoto, Kei

AU - Göransson, Olga

PY - 2012/6/15

Y1 - 2012/6/15

N2 - SIK2 (salt-inducible kinase 2) is a member of the AMPK (AMP-activated protein kinase) family of kinases and is highly expressed in adipocytes. We investigated the regulation of SIK2 in adipocytes in response to cellular stimuli with relevance for adipocyte function and/or AMPK signalling. None of the treatments, including insulin, cAMP inducers or AICAR (5-amino-4- imidazolecarboxamide riboside), affected SIK2 activity towards peptide or protein substrates in vitro. However, stimulation with the cAMP-elevating agent forskolin and the β-adrenergic receptor agonist CL 316,243 resulted in a PKA (protein kinase A)-dependent phosphorylation and 14-3-3 binding of SIK2. Phosphopeptide mapping of SIK2 revealed several sites phosphorylated in response to cAMP induction, including Ser 358. Site-directed mutagenesis demonstrated that phosphorylation of Ser 358, but not the previously reported PKA site Ser 587, was required for 14-3-3 binding. Immunocytochemistry illustrated that the localization of exogenously expressed SIK2 in HEK (human embryonic kidney)-293 cells was exclusively cytosolic and remained unchanged after cAMP elevation. Fractionation of adipocytes, however, revealed a significant increase of wild-type, but not Ser358Ala, HA (haemagglutinin)-SIK2 in the cytosol and a concomitant decrease in a particulate fraction after CL 316,243 treatment. This supports a phosphorylation-dependent relocalization in adipocytes. We hypothesize that regulation of SIK2 by cAMP could play a role for the critical effects of this second messenger on lipid metabolism in adipocytes.

AB - SIK2 (salt-inducible kinase 2) is a member of the AMPK (AMP-activated protein kinase) family of kinases and is highly expressed in adipocytes. We investigated the regulation of SIK2 in adipocytes in response to cellular stimuli with relevance for adipocyte function and/or AMPK signalling. None of the treatments, including insulin, cAMP inducers or AICAR (5-amino-4- imidazolecarboxamide riboside), affected SIK2 activity towards peptide or protein substrates in vitro. However, stimulation with the cAMP-elevating agent forskolin and the β-adrenergic receptor agonist CL 316,243 resulted in a PKA (protein kinase A)-dependent phosphorylation and 14-3-3 binding of SIK2. Phosphopeptide mapping of SIK2 revealed several sites phosphorylated in response to cAMP induction, including Ser 358. Site-directed mutagenesis demonstrated that phosphorylation of Ser 358, but not the previously reported PKA site Ser 587, was required for 14-3-3 binding. Immunocytochemistry illustrated that the localization of exogenously expressed SIK2 in HEK (human embryonic kidney)-293 cells was exclusively cytosolic and remained unchanged after cAMP elevation. Fractionation of adipocytes, however, revealed a significant increase of wild-type, but not Ser358Ala, HA (haemagglutinin)-SIK2 in the cytosol and a concomitant decrease in a particulate fraction after CL 316,243 treatment. This supports a phosphorylation-dependent relocalization in adipocytes. We hypothesize that regulation of SIK2 by cAMP could play a role for the critical effects of this second messenger on lipid metabolism in adipocytes.

KW - 14-3-3

KW - 3T3-l1 adipocyte

KW - cAMP

KW - Insulin

KW - Phosphorylation

KW - Salt-induced kinase (SIK)

UR - http://www.scopus.com/inward/record.url?scp=84862237698&partnerID=8YFLogxK

U2 - 10.1042/BJ20111932

DO - 10.1042/BJ20111932

M3 - Journal article

C2 - 22462548

AN - SCOPUS:84862237698

VL - 444

SP - 503

EP - 514

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 3

ER -

ID: 239566748