Salt-inducible Kinases (SIKs)

SIKs (Salt-inducible kinases) are a family of related serine-threonine kinases. In cultured adrenocortical cells, SIK1 is rapidly but transiently induced by adrenocorticotropin (ACTH) treatment, suggesting that it contributes to ACTH-mediated induction of steroidogenic enzymes. SIK2 is found in adipocytes and phosphorylates a specific serine residue in insulin receptor substrate-1. Members of the SIK family are emerging as important modulators of key processes such as steroid hormone biosynthesis by the adrenal cortex and insulin signaling in adipocytes.

1190378-57-4
MRT67307
1190378-57-4
B0084-474589
HG-9-91-01
1456858-58-4
YKL-05-099
1936529-65-5

Background


An overview of SIKs

Salt-inducible Kinase is a serine/threonine kinase composed of serine/threonine kinase domains located at the n-terminal, sucrose – nonfermenting 1 kinase homologous domain in the middle, and PKA domains dependent on serine residues phosphorylation at the c-terminal.

Major types of SIKs

There are three types of SIK found: SIK1, SIK2, and SIK3. In 1999, Wang obtained SIK1 cDNA from rat adrenal clones using PCR conjugated cDNA abatement hybridization, and discovered that it encodes a new protein kinase, which was named SIK1. Then, based on the structure of SIK1 cDNA, he found two isomers, SIK2 and SIK3, in the human and mouse databases. SIK1 was mainly expressed in the adrenal gland of rats, and small amounts were also found in the brain, pituitary and lungs. SIK2 is expressed exclusively in adipose tissue, especially during the differentiation of fat precursor cells. SIK3 mRNA is generally expressed in various tissues, but its expression is very low.

The inhibitor of SIKs

There are two commonly used inhibitors of SIKs.

I Hg-9-91-01 is an effective selective salt-induced kinase (SIK) inhibitor, acting on SIK1, SIK2 and SIK3, and the IC 50 is at 0.92 nm, 6.6 nm and 9.6 nM respectively.

II Ykl-05-099 is a salt induced kinase (SIK) probe. The IC 50 value of inhibiting SIK2 is 40 nM.

SIKs and disease

It was found that SIKs were involved in the feedback regulation of torc-creb complex activity, and the synthesis of steroid was regulated by CREB, so SIKs could indirectly regulate the synthesis of steroid. It has been reported that SIKs are involved in the regulation of Na +-K -activity in renal epithelial cells and play a key role in the treatment of cardiac hypertrophy and other diseases. Therefore, the research on SIKs has attracted wide attention in the field of medicine.

References:

1. Mischiati, C., Jeang, K. T., Feriotto, G., Breda, L., Borgatti, M., & Bianchi, N., et al. (2001). Aromatic polyamidines inhibiting the tat-induced hiv-1 transcription recognize structured tar-rna. Antisense & Nucleic Acid Drug Development, 11 (4), 209-217.

2. Hamano, T., Murakami, S., Takayama, K., Ehira, S., Maruyama, K., & Kawakami, H., et al. (2004). Characterization of rna-binding properties of three types of rna-binding proteins in anabaena sp. ppc 7120. Cellular and molecular biology (Noisy-le-Grand, France), 50 (5), 613-24.