Downregulation of SIK2 expression promotes the melanogenic program in mice

Horike, Nanao; Kumagai, Akira; Shimono, Yuko; Onishi, Tomoko; Itoh, Yumi; Sasaki, Tsutomu; Kitagawa, Kazuo; Hatano, Osamu; Takagi, Hiroaki; Susumu, Teruo; Teraoka, Hiroshi; Kusano, Ken-ichi; Nagaoka, Yasuo; Kawahara, Hidehisa; Takemori, Hiroshi

doi:10.1111/j.1755-148x.2010.00760.x

Cited by 70 publications

(83 citation statements)

References 58 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro study as well as in vivo analysis using mice with acute SIK2 depletion revealed that SIK2 could be involved in the regulation of gluconeogenesis and lipogenesis in the liver (35). Previous global knockout mice for SIK2 exhibited a neuroprotective effect in brain by activating CREB target genes such as brain-derived neurotrophic factor (BDNF), PPARg coactivator-1a, and B cell lymphoma 2 (Bcl-2) and displayed the increased eumelanin synthesis in their melanocytes (36,38). In this study, we investigated the role of SIK2 in the determination of metabolic phenotype in vivo by using chronic knockout mice.…”

Section: Discussionmentioning

confidence: 99%

“…SIK2 has been implicated in various signaling cascades such as glucose and fat metabolism in the liver, neuroprotective effect in the brain, and the eumelanin synthetic pathway in melanocytes (34)(35)(36)(37)(38). To invariably delineate the functional consequences of the chronic depletion of SIK2 in vivo, we generated knockout mice for SIK2 by deleting two critical exons (exons 2 and 3) from the genomic sequences, resulting in .90% depletion of SIK2 in most tissues as confirmed by quantitative PCR and Western blot analysis (Fig.…”

Section: Sik2 Ko Mice Are Mildly Glucose and Insulin Intolerant But Dmentioning

confidence: 99%

See 1 more Smart Citation

SIK2 Is Critical in the Regulation of Lipid Homeostasis and Adipogenesis In Vivo

et al. 2014

View full text Add to dashboard Cite

Cyclic AMP promotes chronic expression of target genes mainly by protein kinase A–dependent activation of CREB transcription factor machineries in the metabolic tissues. Here, we wanted to elaborate whether CREB-regulated transcription factor (CRTC)2 and its negative regulator salt-inducible kinase (SIK)2 are involved in the transcriptional control of the metabolic pathway in adipocytes. SIK2 knockout (SIK2 KO) mice exhibited higher blood glucose levels that were associated with impaired glucose and insulin tolerance. Hypertriglyceridemia was apparent in SIK2 KO mice, mainly due to the increased lipolysis from white adipocytes and the decreased fatty acid uptake in the peripheral tissues. Investigation of white adipocytes revealed the increases in fat cell size and macrophage infiltration, which could be linked to the metabolic anomaly that is associated in these mice. Interestingly, SIK2 KO promoted the enhancement in the CRTC2-CREB transcriptional pathway in white adipocytes. SIK2 KO mice displayed increased expression of activating transcription factor (ATF)3 and subsequent downregulation of GLUT4 expression and reduction in high–molecular weight adiponectin levels in the plasma, leading to the reduced glucose uptake in the muscle and white adipocytes. The effect of SIK2-dependent regulation of adipocyte metabolism was further confirmed by in vitro cell cultures of 3T3 L1 adipocytes and the differentiated preadipocytes from the SIK2 or CRTC2 KO mice. Collectively, these data suggest that SIK2 is critical in regulating whole-body glucose metabolism primarily by controlling the CRTC2-CREB function of the white adipocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Sik2 Ko Mice Are Mildly Glucose and Insulin Intolerant But Dmentioning

confidence: 99%

SIK2 Is Critical in the Regulation of Lipid Homeostasis and Adipogenesis In Vivo

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Other studies also showed that the insulin-activated SIK2 serves as a repressor of hepatic gluconeogenesis via phosphorylation and translocation of the CREB co-activator TORC2 from the nucleus to the cytoplasm (2,3). In mice, SIK2 was shown to regulate the melanogenesis by modulating the nuclear translocation of TORC1 (4). In adipocytes, SIK2 down-regulates the expression of lipogenic genes, PGC-1␣ and UCP-1 suggesting an involvement in metabolic regulation of adipose tissue (5).…”

Section: Sik2mentioning

confidence: 95%

Interaction between Salt-inducible Kinase 2 and Protein Phosphatase 2A Regulates the Activity of Calcium/Calmodulin-dependent Protein Kinase I and Protein Phosphatase Methylesterase-1

Lee

Yang

Chang

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: SIK2 is the only AMPK family kinase that interacts with PP2A, with a hitherto unknown functional consequences. Results:The interaction between SIK2 and PP2A preserves both enzyme activities and regulates CaMKI and PME-1 negatively. Conclusion:The SIK2⅐PP2A complex is a critical regulator of calcium/calmodulin-mediated activation of CaMKI and PME-1. Significance: SIK2⅐PP2A may play pivotal roles in regulating cell proliferation and stress response.

show abstract

“…Furthermore, SIK2 is known to regulate the initiation of mitosis through phosphorylating the centrosome linker protein, C-Nap1 (5). An intimate link between SIK2 and the CREB coactivator TORC1/2 has also been established, particularly in the contexts of melanogenesis (6,7), cerebral ischemia-associated neuronal survival (8), and corticotropin-releasing hormone transcription (9). However, as an AMPK family kinase, its possible functional link to cellular stress response has not been reported and requires further clarification.…”

Section: Salt-inducible Kinase 2 (Sik2)mentioning

confidence: 99%

Reversible Acetylation Regulates Salt-inducible Kinase (SIK2) and Its Function in Autophagy*

Yang

Tan

Chen

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Salt-inducible kinase (SIK) 2 is an AMP-activated protein kinase family kinase that mediates hormonal and nutrient signaling but has no known link to cellular stress response. Results: p300/CBP and HDAC6 reciprocally regulates Lys-53 acetylation of SIK2, consequently impacting its activity and function in autophagosome maturation. Conclusion: SIK2 kinase activity, via a acetylation-based regulatory switch, contributes to autophagy progression. Significance: SIK2 may be linked to neurodegenerative or protein aggregate disorders.

show abstract

Downregulation of SIK2 expression promotes the melanogenic program in mice

Abstract: ; A y ⁄ ⁄ a mice had brown hair, indicating that SIK2 represses eumelanogenesis in mice.

Cited by 70 publications

References 58 publications

SIK2 Is Critical in the Regulation of Lipid Homeostasis and Adipogenesis In Vivo

SIK2 Is Critical in the Regulation of Lipid Homeostasis and Adipogenesis In Vivo

Interaction between Salt-inducible Kinase 2 and Protein Phosphatase 2A Regulates the Activity of Calcium/Calmodulin-dependent Protein Kinase I and Protein Phosphatase Methylesterase-1

Reversible Acetylation Regulates Salt-inducible Kinase (SIK2) and Its Function in Autophagy*

Contact Info

Product

Resources

About