SIKs (salt-inducible kinases) are evolutionary conserved AMPK (adenosine monophosphate-activated protein kinase) family serine-threonine kinases that were discovered in the adrenal gland of rats given a high-salt diet.1 The SIK subfamily consists of 3 isoforms, SIK1, SIK2, and SIK3, that share a highly homologous N-terminal kinase domain, but their C-terminal regions are less conserved.
2 SIKs are phosphorylated by LKB1 (liver kinase B1), which is thought to be constitutively active, and, therefore, are considered to be constitutively phosphorylated. Additionally, SIKs are phosphorylated at a C-terminal serine residue in response to rises in intracellular cAMP with activation of protein kinase A, though their response to external stimuli is not fully understood.
