High resolution

Module 2: Figure heterotrimeric G protein signalling

Heterotrimeric G proteins function as transducers to activate many signalling pathways.

External stimuli that bind to G protein-coupled receptors (GPCRs) act as guanine nucleotide exchange factors (GEFs) for the heterotrimeric G proteins. When the GDP on the Gα subunit is replaced with GTP, the complex dissociates into Gα/GTP and Gβγ subunits that are then capable of activating or inhibiting a wide range of signalling systems. Most of the actions are stimulatory, but some are inhibitory, as illustrated by the yellow arrows. The regulators of G protein signalling (RGS) proteins function as GTPase-activating proteins (GAPs) to facilitate the GTPase activity of the Gα subunit, which is the OFF reaction that terminates signalling. G protein receptor kinase (GRK) phosphorylates active receptors and provides binding sites for arrestin that result in receptor desensitization by preventing the heterotrimeric G proteins from binding the receptor.