Salt-inducible kinase

Salt-inducible kinases, also known as SIK enzymes, are a family of proteins found in most animal species. They are a type of serine-threonine kinase enzymes. They were originally isolated from the adrenal glands of rats fed with a high-salt diet. SIK enzymes are part of a system of proteins which act as a sensor of intracellular sodium levels and activate the Na(+),K(+)-ATPase to expel excess sodium from the cytosol, which is then excreted in urine by the kidneys. There are three subtypes, SIK1, SIK2 and SIK3. SIK1 is induced by cAMP and represses the activity of CRE-binding protein (CREB). SIK1 is also involved with regulating steroidogenic enzyme production during steroidogenesis. In recent years, SIK enzymes have attracted interest as a potential target for anti-cancer drugs,[1] as well as playing a role in other processes such as hypertension and acute kidney injury. They are also involved in the tanning response following UV exposure.[2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]

Inhibitors

References

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  3. ^ Takemori H, Okamoto M (February 2008). "Regulation of CREB-mediated gene expression by salt inducible kinase". The Journal of Steroid Biochemistry and Molecular Biology. 108 (3–5): 287–291. doi:10.1016/j.jsbmb.2007.09.006. PMID 17935972.
  4. ^ Jaitovich A, Bertorello AM (December 2010). "Intracellular sodium sensing: SIK1 network, hormone action and high blood pressure". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1802 (12): 1140–1149. doi:10.1016/j.bbadis.2010.03.009. PMID 20347966.
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  6. ^ Du WQ, Zheng JN, Pei DS (2016). "The diverse oncogenic and tumor suppressor roles of salt-inducible kinase (SIK) in cancer". Expert Opinion on Therapeutic Targets. 20 (4): 477–485. doi:10.1517/14728222.2016.1101452. PMID 26549013.
  7. ^ Taub M (July 2018). "Gene Level Regulation of Na,K-ATPase in the Renal Proximal Tubule Is Controlled by Two Independent but Interacting Regulatory Mechanisms Involving Salt Inducible Kinase 1 and CREB-Regulated Transcriptional Coactivators". International Journal of Molecular Sciences. 19 (7): 2086. doi:10.3390/ijms19072086. PMC 6073390. PMID 30021947.
  8. ^ Chen F, Chen L, Qin Q, Sun X (2019). "Salt-Inducible Kinase 2: An Oncogenic Signal Transmitter and Potential Target for Cancer Therapy". Frontiers in Oncology. 9: 18. doi:10.3389/fonc.2019.00018. PMC 6349817. PMID 30723708.
  9. ^ Taub M (June 2019). "Salt Inducible Kinase Signaling Networks: Implications for Acute Kidney Injury and Therapeutic Potential". International Journal of Molecular Sciences. 20 (13): 3219. doi:10.3390/ijms20133219. PMC 6651122. PMID 31262033.
  10. ^ Sun Z, Jiang Q, Li J, Guo J (August 2020). "The potent roles of salt-inducible kinases (SIKs) in metabolic homeostasis and tumorigenesis". Signal Transduction and Targeted Therapy. 5 (1): 150. doi:10.1038/s41392-020-00265-w. PMC 7423983. PMID 32788639.
  11. ^ Darling NJ, Cohen P (April 2021). "Nuts and bolts of the salt-inducible kinases (SIKs)". The Biochemical Journal. 478 (7): 1377–1397. doi:10.1042/BCJ20200502. PMC 8057676. PMID 33861845.
  12. ^ Yardman-Frank JM, Fisher DE (April 2021). "Skin pigmentation and its control: From ultraviolet radiation to stem cells". Experimental Dermatology. 30 (4): 560–571. doi:10.1111/exd.14260. PMC 8218595. PMID 33320376.
  13. ^ António T, Soares-da-Silva P, Pires NM, Gomes P (October 2022). "Salt-inducible kinases: new players in pulmonary arterial hypertension?". Trends in Pharmacological Sciences. 43 (10): 806–819. doi:10.1016/j.tips.2022.06.008. PMID 35851157.
  14. ^ Jagannath A, Taylor L, Ru Y, Wakaf Z, Akpobaro K, Vasudevan S, et al. (July 2023). "The multiple roles of salt-inducible kinases in regulating physiology". Physiological Reviews. 103 (3): 2231–2269. doi:10.1152/physrev.00023.2022. PMC 10190946. PMID 36731029.
  15. ^ Feng S, Wei F, Shi H, Chen S, Wang B, Huang D, et al. (November 2023). "Roles of salt‑inducible kinases in cancer (Review)". International Journal of Oncology. 63 (5). doi:10.3892/ijo.2023.5566. PMC 10546379. PMID 37654200.
  16. ^ Shreberk-Hassidim R, Ostrowski SM, Fisher DE (February 2023). "The Complex Interplay between Nevi and Melanoma: Risk Factors and Precursors". International Journal of Molecular Sciences. 24 (4): 3541. doi:10.3390/ijms24043541. PMC 9964821. PMID 36834954.
  17. ^ Shi F (2024). "Understanding the roles of salt-inducible kinases in cardiometabolic disease". Frontiers in Physiology. 15: 1426244. doi:10.3389/fphys.2024.1426244. PMC 11286596. PMID 39081779.
  18. ^ Manoharan R (January 2025). "Salt-inducible kinases (SIKs) in cancer: mechanisms of action and therapeutic prospects". Drug Discovery Today. 30 (1): 104279. doi:10.1016/j.drudis.2024.104279. PMID 39710233.
  19. ^ Onda DA, Zhu Y, Yuan X, Loh K (February 2025). "Central and Peripheral Roles of Salt-inducible Kinases in Metabolic Regulation". Endocrinology. 166 (3). doi:10.1210/endocr/bqaf024. PMID 39919030.
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