Figure 1 The role of GPCRs in the regulation of human physiology Figure 1 | The role of GPCRs in the regulation of human physiology. Following the binding of ligands, G protein-coupled receptors (GPCRs) undergo conformational changes that promote the exchange of GDP with GTP on the α subunit of heterotrimeric G proteins (composed of α, β and γ subunits). This event causes the dissociation of Gα from the dimer Gβγ, leading to the activation of several downstream signalling pathways, involving, for example, second messengers (adenylyl and guanylyl cyclases and phosphatidylinositols), protein kinases (protein kinase G (PKG), protein kinase A (PKA) and protein kinase C (PKC)), phospholipases, Rho GTPases (for example, RHOA) and intracellular calcium ions (Ca2+). These mechanisms mediate different biological processes, ranging from vasodilatation and bronchodilation to neuroendocrine regulation of immune responses (shown in the coloured boxes). AT1R, type 1 angiotensin II receptor; β1AR, β1 adrenergic receptor; β2AR, β2 adrenergic receptor; cAMP, cyclic adenosine monophosphate; CaSR, calcium-sensing receptor; cGMP, cyclic guanosine monophosphate; DAG, diacylglycerol; ERK 1/2, extracellular signal-regulated kinase 1/2; ETAR, endothelin receptor type A; M3, muscarinic acetylcholine receptor 3; RHOGEF, Rho guanine nucleotide exchange factor; ROS, reactive oxygen species; TSHR, thyroid stimulating hormone receptor; VCAM1, vascular cell adhesion protein 1. Cabral-Marques, O. & Riemekasten, G. (2017) Functional autoantibodies targeting G protein-coupled receptors in rheumatic diseases Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2017.134