Ask about this productRelated genes to: Sik1 antibody
- Gene:
- SIK1 NIH gene
- Name:
- salt inducible kinase 1
- Previous symbol:
- SNF1LK
- Synonyms:
- msk
- Chromosome:
- 21q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 2000-05-23
- Date modifiied:
- 2015-11-23
Related products to: Sik1 antibody
Related articles to: Sik1 antibody
- The protein arginine methyl transferase 5 (PRMT5) emerges as a therapeutic target in S-methyl-5'-thioadenosine phosphorylase (MTAP)-deleted cancers, where 5'-methylthioadenosine (MTA) accumulation partially inhibits its activity. However, it remains unclear whether other genetic alterations can dictate PRMT5 activity in cancer. Here, we identify liver kinase B1 (LKB1) as an alternative predictor of PRMT5 inhibition in lung cancer independent of MTAP. Mechanistically, LKB1 loss activates salt-inducible kinase 1/2 (SIK1/2)-cAMP response element-binding protein-regulated transcription coactivator 2 (CRTC2) signaling to upregulate nicotinamide N-methyltransferase (NNMT), creating a "methyl sink" that lowers the S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) ratio and attenuates PRMT5 activity. NNMT overexpression is sufficient to induce this hypomorphic PRMT5 state and heighten sensitivity to PRMT5 inhibitors. Functionally, PRMT5 inhibition induces senescence in LKB1-deficient cells and confers vulnerability to navitoclax, synergistically blunting tumor growth in vivo. Collectively, we identify PRMT5 as an actionable therapeutic vulnerability in LKB1-deficient lung cancer, and propose LKB1 status/NNMT expression as potential biomarkers for PRMT5 inhibition. These findings may expand the clinical utility of PRMT5-targeted therapies beyond MTAP-deleted cancers. - Source: PubMed
Publication date: 2026/06/02
Mi WenXia XinyiXue YunLi LiuchengYang LiYang XinchengXu JieCai XinleiZhou YijiaZhu LingzhiWang GuanlinLi FeiJi HongbinTong XinyuanLiu PingyuLi Fuming - Metabolic dysfunction-associated steatotic liver disease (MASLD) constitutes a chronic inflammatory condition within the spectrum of metabolic liver diseases, characterized by the accumulation of hepatic lipids in the absence of significant alcohol consumption, however, the contribution of PANoptosis to its pathobiology remains largely undefined. - Source: PubMed
Publication date: 2026/05/26
Zhang HongLiu XinLiu YanGong DacaiLai MinGe BinWang DanTan MingshengChen Peng - The Hippo signaling pathway is a highly conserved pathway in metazoans that limits organ size by restricting tissue overgrowth. This pathway is named after one of its key components, the Ste20 family protein kinase Hippo (Hpo). We previously identified SIK1 in Arabidopsis as a functional orthologue of Hpo and Ste20 and found that the sik1 mutant has smaller lateral organs due to cell cycle exit failure and delayed onset of cell expansion. The plant hormone jasmonic acid (JA) can limit cell proliferation and organ growth, and studies including our own have shown a potential association between SIK1 and JA. In this study, we investigated whether SIK1 is involved in JA biosynthesis, signaling, or response. We found that under normal growth conditions, JA levels and responses were elevated in sik1. However, the JA biosynthetic mutants aos and opr3, as well as the JA receptor mutant coi1, could not suppress the dwarf phenotype of sik1, indicating that the elevated JA response was not the cause of the reduced organ size in sik1. On the other hand, sik1, aos sik1, and opr3 sik1 mutants were all hypersensitive to exogenous JA in primary root elongation, whereas coi1 sik1, like coi1, was insensitive to JA. Furthermore, we found that SIK1 interacts with COI1 both in vitro and in vivo, and negatively regulates the JA response. RNA sequencing analyses further validated that the dwarf phenotype of sik1 was not a result of elevated JA response, but rather, may be due to a failure in cell cycle exit as we had previously reported. Our findings revealed two separate roles of SIK1; it plays a direct positive role in organ size control and a negative role in JA response which is achieved at least partially through its interaction with COI1. - Source: PubMed
Publication date: 2026/05/23
Wang QinyingZhang PingpingYang YiWang GuipingXin PeiyongChu JinfangWu ShianGong Qingqiu - The paraventricular nucleus (PVN) plays a pivotal role in integrating neuroendocrine responses to stress, with the salt-inducible kinase 1 (SIK1)-CREB-regulated transcription co-activator 1 (CRTC1) pathway critically regulating corticotropin-releasing hormone expression and hypothalamic-pituitary-adrenal (HPA) axis activity. Mirtazapine is a clinically effective antidepressant with a unique noradrenergic and specific serotonergic mechanism, yet whether its therapeutic actions involve modulation of this PVN pathway remains unexplored. - Source: PubMed
Publication date: 2026/05/25
Zhang HaiboDong HongliXi ZhengrongYan ZhimeiZhang YalinZhang Lin - Excessive lipid accumulation in skeletal muscle contributes to insulin resistance. Salt-inducible kinase 1 (SIK1) is known to be involved in myogenic differentiation, yet its role in lipid-induced skeletal muscle insulin resistance remains unclear. Here, we identified the functional role of SIK1 in skeletal muscle insulin resistance under lipid overload and delineated the underlying signaling mechanisms. In C2C12 myotubes, palmitate markedly increased SIK1 expression and phosphorylation at Thr182, and further impaired insulin-stimulated Akt phosphorylation and glucose uptake. These effects were blocked by SIK1 knockdown or pharmacological inhibition of SIK. The palmitate-induced upregulation of SIK1 and the associated insulin signaling defects were abolished by inhibition of TGFβ receptor 1 or knockdown of Smad2/3. Moreover, genetic or pharmacological inhibition of SIK1 restored the palmitate-reduced cAMP levels in myotubes, and inhibition of PDE4 similarly rescued cAMP levels and insulin signaling, mimicking the effects of SIK1 suppression. Consistent with these in vitro findings, SIK1 and TGFβ1-Smad2/3 signaling were upregulated while cAMP levels were decreased in skeletal muscle of diet-induced obese (DIO) mice. Either SIK inhibition or blockade of TGFβ1-Smad2/3 signaling restored the impaired insulin-stimulated Akt phosphorylation in isolated skeletal muscle. Together, we demonstrate that SIK1 is upregulated under lipid overload via TGFβ1-Smad2/3 signaling, thereby triggering PDE4-dependent cAMP degradation and consequent insulin resistance in skeletal muscle. These findings establish SIK1 as a critical mediator of lipid overload-induced insulin signaling defects in skeletal muscle. - Source: PubMed
Publication date: 2026/03/17
Liu YanliShi YuShen YuQu HuiQin LiHuang SulingLeng Ying