Salt-inducible kinase (SIK) isoforms: their involvement in steroidogenesis and adipogenesis

Katoh, Yoshiko; Takemori, Hiroshi; Horike, Nanao; Doi, Junko; Muraoka, Masaaki; Li, Min; Okamoto, Mitsuhiro

doi:10.1016/j.mce.2003.10.016

Cited by 96 publications

(86 citation statements)

References 9 publications

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“…SIK3 belongs to the SIK subfamily, which also includes SIK1 (also known as MSK or SNF1LK) and SIK2 (also known as QIK) (Katoh et al, 2004). Mammalian SIK1 and SIK2 are currently being characterized in terms of their function in various biological processes and molecular regulatory mechanisms.…”

Section: Introductionmentioning

confidence: 99%

SIK3 is essential for chondrocyte hypertrophy during skeletal development in mice

et al. 2012

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SUMMARYChondrocyte hypertrophy is crucial for endochondral ossification, but the mechanism underlying this process is not fully understood. We report that salt-inducible kinase 3 (SIK3) deficiency causes severe inhibition of chondrocyte hypertrophy in mice. SIK3-deficient mice showed dwarfism as they aged, whereas body size was unaffected during embryogenesis. Anatomical and histological analyses revealed marked expansion of the growth plate and articular cartilage regions in the limbs, accumulation of chondrocytes in the sternum, ribs and spine, and impaired skull bone formation in SIK3-deficient mice. The primary phenotype in the skeletal tissue of SIK3-deficient mice was in the humerus at E14.5, where chondrocyte hypertrophy was markedly delayed. Chondrocyte hypertrophy was severely blocked until E18.5, and the proliferative chondrocytes occupied the inside of the humerus. Consistent with impaired chondrocyte hypertrophy in SIK3-deficient mice, native SIK3 expression was detected in the cytoplasm of prehypertrophic and hypertrophic chondrocytes in developing bones in embryos and in the growth plates in postnatal mice. HDAC4, a crucial repressor of chondrocyte hypertrophy, remained in the nuclei in SIK3-deficient chondrocytes, but was localized in the cytoplasm in wild-type hypertrophic chondrocytes. Molecular and cellular analyses demonstrated that SIK3 was required for anchoring HDAC4 in the cytoplasm, thereby releasing MEF2C, a crucial facilitator of chondrocyte hypertrophy, from suppression by HDAC4 in nuclei. Chondrocyte-specific overexpression of SIK3 induced closure of growth plates in adulthood, and the SIK3-deficient cartilage phenotype was rescued by transgenic SIK3 expression in the humerus. These results demonstrate an essential role for SIK3 in facilitating chondrocyte hypertrophy during skeletogenesis and growth plate maintenance.

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Section: Introductionmentioning

confidence: 99%

SIK3 is essential for chondrocyte hypertrophy during skeletal development in mice

et al. 2012

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“…IRS-1 deficiency in embryonic fibroblast cells leads to inhibition of adipogenesis in these cells [14]. There are serine/threonine phosphorylation sites in IRS-1, and the phosphorylation of these sites inhibits IRS-1 [15][16][17], leading to insulin resistance. IRS-1 is therefore related to obesity and diabetes [18,19].…”

Section: Introductionmentioning

confidence: 99%

Protein kinase A suppresses the differentiation of 3T3-L1 preadipocytes

Wang

Zhou

et al. 2008

Cell Res

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cAMP and protein kinase A (PKA) are widely known as signaling molecules that are important for the induction of adipogenesis. Here we show that a strong increase in the amount of cAMP inhibits the adipogenesis of 3T3-L1 fibroblast cells. Stimulation of PKA activity suppresses adipogenesis and, in contrast, inhibition of PKA activity markedly accelerates the adipogenic process. As adipogenesis progresses, there is a significant increase in the expression level of PKA regulatory subunits and a corresponding decrease in PKA activity. Moreover, treatment of 3T3-L1 cells with epidermal growth factor (EGF) stimulates PKA activity and blocks adipogenesis. Inhibition of PKA activity abolishes this suppressive effect of EGF on adipogenesis. Moreover, activation of PKA induces serine/threonine phosphorylation, reduces tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) and the association between PKA and IRS-1. Taken together, our study demonstrates that PKA has a pivotal role in the suppression of adipogenesis. cAMP at high concentrations can suppress adipogenesis through PKA activation. These findings could be important and useful for understanding the mechanisms of adipogenesis and the relevant physiological events.

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“…This subfamily is conserved from Caenorhabditis elegans to humans, and there are three members in mammals (41,42). SIK1 was initially identified as a protein up-regulated in the adrenal glands of rats fed a high salt diet as well as in PC12 cells upon neuronal depolarization (43,44).…”

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confidence: 99%

“…Chicken SIK1 was also cloned as a product induced by a winged helix transcription factor (45). Two SIK1 paralogs, SIK2 and SIK3 (also known as QSK), were found by database search based on sequence similarity (41). The three kinases share the catalytic domain located at the N-terminal part but show divergence in other regions.…”

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confidence: 99%

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The Tumor Suppressor Kinase LKB1 Activates the Downstream Kinases SIK2 and SIK3 to Stimulate Nuclear Export of Class IIa Histone Deacetylases

Walkinshaw

Weist

Kim

et al. 2013

Journal of Biological Chemistry

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Background: HDAC4, -5, -7, and -9 possess conserved motifs for phosphorylation-dependent 14-3-3 binding. Results: SIK2 and SIK3 phosphorylate the deacetylases at the motifs to stimulate 14-3-3 binding. Conclusion:The tumor suppressor kinase LKB1 activates SIK2 and SIK3 to promote trafficking of class IIa HDACs. Significance: This study indicates that LKB1-dependent SIK activation is an important module upstream from class IIa HDACs.

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Salt-inducible kinase (SIK) isoforms: their involvement in steroidogenesis and adipogenesis

Cited by 96 publications

References 9 publications

SIK3 is essential for chondrocyte hypertrophy during skeletal development in mice

SIK3 is essential for chondrocyte hypertrophy during skeletal development in mice

Protein kinase A suppresses the differentiation of 3T3-L1 preadipocytes

The Tumor Suppressor Kinase LKB1 Activates the Downstream Kinases SIK2 and SIK3 to Stimulate Nuclear Export of Class IIa Histone Deacetylases

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