Gq11

Gq11, also called G alpha-11 (encoded by the GNA11 gene), is a member of the G protein alpha subunits that form part of the Gq/11 family. It functions as part of heterotrimeric G proteins that relay signals from activated G protein-coupled receptors (GPCRs) to downstream effectors, thereby translating extracellular cues into intracellular responses.

In the resting state, Gq11 is bound to GDP and associated with the G beta-gamma subunits. Upon GPCR activation, a guanine nucleotide exchange prompts Gq11 to release GDP and bind GTP, causing the alpha subunit to dissociate from G beta-gamma. Gq11 then interacts with and activates phospholipase C beta (PLCβ), which hydrolyzes phosphatidylinositol 4,5-bisphosphate to generate inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 elevates intracellular calcium, while DAG activates protein kinase C (PKC) and related signaling pathways. The GTPase activity of Gq11 eventually converts GTP back to GDP, allowing Gq11 to reassociate with G beta-gamma and terminate the signal.

Gq11 is widely expressed, with notable presence in various tissues including brain, smooth muscle, platelets, and melanocytes. It couples to a broad range of GPCRs that respond to neurotransmitters, hormones, and other signals, thereby influencing processes such as calcium signaling, secretion, muscle contraction, and cell proliferation.

Clinical significance centers on cancer biology, particularly uveal melanoma. Activating somatic mutations in GNA11 have been identified in a subset of uveal melanomas and are often mutually exclusive with mutations in GNAQ, another Gq family member. These mutations lead to constitutive PLCβ signaling and downstream pathway activation, contributing to tumorigenesis. Therapeutic approaches targeting downstream effectors of Gq11 signaling, such as PKC or MAPK pathways, are under investigation.