Fig. 2.

General principle of signaling by PTHR. Following ligand binding, the receptor undergoes conformational changes, which promote the coupling with heterotrimeric G proteins (Gαβγ), and catalyzes the exchange of GDP for GTP on the α-subunit. This event triggers conformational and/or dissociation events between the α- and βγ subunits. Gα_S activates adenylyl cyclases leading to cAMP synthesis, which in turn activates protein kinase A (PKA). Gαq activates phospholipase C, which cleaves phosphatidylinositol (4,5)-bisphosphate (PIP₂) into diacylglycerol (DAG) and inositol (1,4,5)-trisphosphate (IP₃). IP₃ then diffuses through the cytosol and activates IP₃-gated Ca²⁺ channels in the membranes of the endoplasmic reticulum, causing the release of stored Ca²⁺ into the cytosol. The increase of cytosolic Ca²⁺ promotes PKC translocation to the plasma membrane, and then activation by DAG