Fig. 4.
Proposed model underlying Gq/11-mediated enhancement of PTHR endosomal cAMP. Binding of PTH to the PTHR results in activation of heterotrimeric Gs and Gq proteins at the cell surface, resulting in stimulation of adenylyl cyclase (1) and PLCβ (2) via GαS and Gαq, respectively. In addition, liberation of Gβγ subunits specifically from Gαq promotes PI3Kβ-dependent generation of PI(3,4,5)P3 (3), which subsequently facilitates βarr recruitment to the PTHR (4) and formation of ternary PTHR–βarr–Gβγ complexes that remain active following translocation from the cell surface to early endosomes (5), and thus permit a sustained phase of cAMP production (6).