The Role of the Salt-inducible Kinases in the Endocrine Glands

The salt-inducible kinases (SIKs), a family of serine/threonine kinases, are emerging endocrine regulators. The 3 isoforms, SIK1, SIK2, and SIK3, compose a subfamily of the 5' adenosine monophosphate-activated protein kinase-related kinases. The SIKs have multiple conserved protein kinase A phosphorylation sites by which they are regulated. Further, a family of well-characterized SIK targets is the cAMP response element binding protein regulated transcription coactivators, which promote cAMP response element-binding protein transcription. As such, the SIKs participate in several cAMP-dependent pathways, including classical GPCR cascades characteristic of endocrine signaling. This review discusses the currently known roles of the SIKs in the endocrine system. Specifically, the research on SIKs in this field up to this point has focused on the adrenal glands, ovary, pancreas, pineal gland, immune function of the thymus, parathyroid hormone signaling in the bone, and hypothalamic regulation of the circadian rhythm and endocrine axes. Furthermore, this review highlights the remaining questions in these areas and the glands in which little to no SIK research has been published: the testis, pituitary, thyroid gland, and parathyroid glands.