Pathways /
G-protein signaling
Overview
The guanine nucleotide-binding protein (G-protein) cell signaling pathway functions in metabolic regulation, neurotransmission, and embryonic development. The G-protein signaling pathway may be activated by a ligand binding to the G-protein coupled receptor (GPCR). The pathway may be inhibited by phosphorylation of the GPCR by protein kinases and the subsequent binding of arrestin proteins. [1]

Figure 1. Binding of a growth factor (e.g., EGF, HGF) to the G-protein coupled receptor (GPCR) causes a conformational change in the GPCR. The conformational change in the GPCR activates a trimeric GTP binding protein (e.g., GNA11 and GNAQ), resulting in GDP dissociation, GTP association, and resultant activation. The active G-protein regulates activity of target proteins in the cell membrane. Activated target proteins relay signals to other proteins to initiate gene transcription, metabolic regulation, cell growth, and survival. G-protein inactivation occurs when GTP is exchanged for GDP. Specific nodes in the pathway that are therapeutically actionable are noted.