Salt inducible kinases and PTH1R action.

Parathyroid hormone is a central regulator of calcium homeostasis. PTH protects the organism from hypocalcemia through its actions in bone and kidney. Recent physiologic studies have revealed key target genes for PTH receptor (PTH1R) signaling in these target organs. However, the complete signal transduction cascade used by PTH1R to accomplish these physiologic actions has remained poorly defined. Here we will review recent studies that have defined an important role for salt inducible kinases downstream of PTH1R in bone, cartilage, and kidney. PTH1R signaling inhibits the activity of salt inducible kinases. Therefore, direct SIK inhibitors represent a promising novel strategy to mimic PTH actions using small molecules. Moreover, a detailed understanding of the molecular circuitry used by PTH1R to exert its biologic effects will afford powerful new models to better understand the diverse actions of this important G protein coupled receptor in health and disease.