SIK
Within the AMPK family, the subfamily of salt inducible kinases (SIKs) contains three kinases (SIK1–3). SIK1, the founding member of this subfamily, was identified and named as a kinase whose expression is induced in the adrenal gland of rats fed a high salt diet. Subsequent homology searches led to the identification of SIK2 and SIK3. All three SIK family members share a characteristic structure, including an N-terminal kinase domain bearing a LKB1 phosphorylation site, a sucrose non-fermenting-1 (SNF-1) homology domain, and a long C-terminal extension containing multiple potential protein kinase A phosphorylation sites. All three SIK family kinases are expressed broadly. SIK1 mRNA expression is regulated by multiple stimuli, including high dietary salt intake, ACTH signaling, glucagon signaling, excitable cell depolarization, and circadian rhythms. In contrast, SIK2 and SIK3 expression is constitutive in tissues in which these kinases are expressed. In humans, SIK2 and SIK3 are expressed ubiquitously, with highest SIK2 levels in adipose tissue and highest SIK3 expression in brain. Interestingly, SIK2 and SIK3 are closely linked on human chromosome 11 and mouse chromosome 9. A key role of SIKs is to control dynamic changes in phosphorylation and subcellular localization of class IIa HDACs and CRTC factors. Signals that increase intracellular cAMP levels lead to protein kinase A (PKA)-mediated SIK family member phosphorylation. PKA-mediated phosphorylation does not alter SIK intrinsic kinase activity. However, mutation of PKA phosphoacceptor sites leads to SIK variants whose cellular activity cannot be inhibited by cAMP-inducing signals. PKA-mediated SIK phosphorylation promotes interaction between SIK and 14–3–3 proteins. This PKA-inducible SIK/14–3–3 association leads to conformational changes and/or shifts in SIK cytoplasmic distribution which block the ability of these kinases to access and phosphorylate their substrates.
References
1.Wein MN,et al. Trends Endocrinol Metab. 2018 Oct; 29(10): 723–735.
References
1.Wein MN,et al. Trends Endocrinol Metab. 2018 Oct; 29(10): 723–735.
Autophagy
SIK
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GLPG3970
产品货号 : M36521
cas no: 2403733-82-2
GLPG3970 (compound 88) 是一类首创的 SIK2/SIK3 抑制剂。GLPG3970 可用于炎症和自身免疫性疾病的研究。 -
MRT 67307 dihydrochloride
产品货号 : M34901
cas no: 1781882-89-0
MRT67307 dihydrochloride 是 IKKε 和 TBK-1 的双抑制剂,IC50 分别为 160 和 19 nM。MRT67307 dihydrochloride 也可抑制 ULK1 和 ULK2,IC50 分别为 45 和 38 nM。MRT67307 dihydrochloride 还抑制细胞自噬 (autophagy)。 -
YKL-06-062
产品货号 : M33533
cas no: 2172617-16-0
YKL-06-062 是第二代 salt-inducible kinase (SIK) 抑制剂,抑制 SIK1, SIK2 和 SIK3 的 IC50 为 2.12 nM/1.40 nM/2.86 nM。 -
WH-4-025
产品货号 : M23855
cas no: 1876463-35-2
WH-4-025 是一种盐诱导激酶 (SIK) 抑制剂。 -
Dp44mT
产品货号 : M18062
cas no: 152095-12-0
Dp44mT 是一种有效的铁螯合剂,具有选择性抗肿瘤活性。