Insulin induces Thr484 phosphorylation and stabilization of SIK2 in adipocytes

Säll, Johanna; Negoita, Florentina; Hansson, Björn; Kopietz, Franziska; Linder, Wilhelm; Pettersson, Anna; Ekelund, Mikael; Laurencikiene, Jurga; Degerman, Eva; Stenkula, Karin G.; Göransson, Olga

doi:10.1016/j.cellsig.2018.12.011

Cited by 4 publications

(4 citation statements)

References 21 publications

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“…Indeed, SIK2 expression and function are inversely correlated with insulin resistance and obesity in humans 12 , 29 . While inhibition of SIK2 in macrophages appears to promote the release of anti-inflammatory cytokines 48 , adipocyte SIK2 has been found to regulate Glut4 expression and insulin signaling 28 .…”

Section: Discussionmentioning

confidence: 99%

Activation of the adipocyte CREB/CRTC pathway in obesity

et al. 2021

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Obesity is a major risk factor for the development of type II diabetes. Increases in adipose tissue mass trigger insulin resistance via the release of pro-inflammatory cytokines from adipocytes and macrophages. CREB and the CRTC coactivators have been found to promote insulin resistance in obesity, although the mechanism is unclear. Here we show that high fat diet feeding activates the CREB/CRTC pathway in adipocytes by decreasing the expression of SIK2, a Ser/Thr kinase that phosphorylates and inhibits CRTCs. SIK2 levels are regulated by the adipogenic factor C/EBPα, whose expression is reduced in obesity. Exposure to PPARγ agonist rescues C/EBPα expression and restores SIK2 levels. CRTC2/3 promote insulin resistance via induction of the chemokines CXCL1/2. Knockout of CRTC2/3 in adipocytes reduces CXCL1/2 expression and improves insulin sensitivity. As administration of CXCL1/2 reverses salutary effects of CRTC2/3 depletion, our results demonstrate the importance of the CREB/CRTC pathway in modulating adipose tissue function.

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Section: Discussionmentioning

confidence: 99%

Activation of the adipocyte CREB/CRTC pathway in obesity

et al. 2021

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“…What is more, SIK1 and SIK3 play an important role in immune regulation 12,13 . SIK2 widely expresses in human and mouse adipose tissues, which mainly participates in the regulation of glucose and lipid metabolism through phosphorylation 14–17 . Furthermore, SIK2 has important roles in cell cycle, tumor, melanogenesis, neuronal damage repair, and apoptosis 18–21 .…”

Section: Introductionmentioning

confidence: 99%

“… 12 , 13 SIK2 widely expresses in human and mouse adipose tissues, which mainly participates in the regulation of glucose and lipid metabolism through phosphorylation. 14 , 15 , 16 , 17 Furthermore, SIK2 has important roles in cell cycle, tumor, melanogenesis, neuronal damage repair, and apoptosis. 18 , 19 , 20 , 21 Recent studies showed that SIK2 regulates the macrophage polarization to make a balance between inflammation and macrophage, 9 , 22 given the function of macrophage, which indicate that SIK2 might be involved in the regulation of immune response.…”

Section: Introductionmentioning

confidence: 99%

Deficiency of salt‐inducible kinase 2 (SIK2) promotes immune injury by inhibiting the maturation of lymphocytes

Zhu,

Li,

Wang

et al. 2023

MedComm

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Salt‐inducible kinase 2 (SIK2) belongs to the serine/threonine protein kinases of the AMPK/SNF1 family, which has important roles in cell cycle, tumor, melanogenesis, neuronal damage repair and apoptosis. Recent studies showed that SIK2 regulates the macrophage polarization to make a balance between inflammation and macrophage. Macrophage is critical to initiate immune regulation, however, whether SIK2 can be involved in immune regulation is not still well understood. Here, we revealed that the protein of SIK2 was highly expressed in thymus, spleen, lung, and brain. And SIK2 protein content increased in RAW264.7 and AHH1 cells with a time and dose‐dependent after‐ionizing radiation (IR). Inhibition of SIK2 could promote AHH1 cells apoptosis Moreover, we used the Cre‐LoxP system to construct the SIK2+/− mice, and the research on function suggested that the deficiency of SIK2 could promote the sensitivity of IR. The deficiency of SIK2 promoted the immune injury via inhibiting the maturation of T cells and B cells. Furthermore, the TCRβ rearrangement was inhibited by the deficiency of SIK2. Collectively, this study demonstrated that SIK2 provides an essential function of regulating immune injury, which will provide new ideas for the treatment of immune injury‐related diseases.

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“…Subsequent homology searches led to the identification of SIK2 and SIK3 and all three SIK family kinases are expressed broadly (3)(4)(5). As an isoform of the SIK family, SIK2 modulates various biological functions and acts as a signal transmitter in various pathways (3,6). Compared with that in adjacent normal tissues, the expression of SIK2 is significantly higher in multiple types of tumors, which indicates its pivotal effect in oncogenesis (7).…”

Section: Introductionmentioning

confidence: 99%