Salt-Inducible Kinases: Physiology, Regulation by cAMP, and Therapeutic Potential

Marc N Wein; Marc Foretz; David E Fisher; Ramnik J Xavier; Henry M Kronenberg

doi:10.1016/j.tem.2018.08.004

Salt-Inducible Kinases: Physiology, Regulation by cAMP, and Therapeutic Potential

Trends Endocrinol Metab. 2018 Oct;29(10):723-735. doi: 10.1016/j.tem.2018.08.004. Epub 2018 Aug 24.

Authors

Marc N Wein¹, Marc Foretz², David E Fisher³, Ramnik J Xavier⁴, Henry M Kronenberg⁵

Affiliations

¹ Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: mnwein@partners.org.
² INSERM, U1016, Institut Cochin, Paris 75014, France; CNRS, UMR8104, Paris 75014, France; Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France.
³ Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁵ Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

Salt-inducible kinases (SIKs) represent a subfamily of AMP-activated protein kinase (AMPK) family kinases. Initially named because SIK1 (the founding member of this kinase family) expression is regulated by dietary salt intake in the adrenal gland, it is now apparent that a major biological role of these kinases is to control gene expression in response to extracellular cues that increase intracellular levels of cAMP. Here, we review four physiologically relevant examples of how cAMP signaling impinges upon SIK cellular function. By focusing on examples of cAMP-mediated SIK regulation in gut myeloid cells, bone, liver, and skin, we highlight recent advances in G protein-coupled receptor (GPCR) signal transduction. New knowledge regarding the role of SIKs in GPCR signaling has led to therapeutic applications of novel small molecule SIK inhibitors.

Keywords: glucose metabolism; inflammation; kinase; osteoporosis; second messengers; skin pigmentation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

AMP-Activated Protein Kinases / antagonists & inhibitors
AMP-Activated Protein Kinases / metabolism*
Humans
Protein Kinase Inhibitors / therapeutic use*
Protein Kinases / metabolism*
Protein Serine-Threonine Kinases / antagonists & inhibitors
Protein Serine-Threonine Kinases / metabolism*
Receptors, G-Protein-Coupled / metabolism*
Signal Transduction / physiology*

Substances

Protein Kinase Inhibitors
Receptors, G-Protein-Coupled
Protein Kinases
salt-inducible kinase-2, human
Protein Serine-Threonine Kinases
SIK1 protein, human
SIK3 protein, human
AMP-Activated Protein Kinases

Abstract

Publication types

MeSH terms

Substances

Grants and funding