Gq11mediated

Gq11-mediated signaling refers to cellular signaling driven by the G protein alpha subunits of the Gq family, chiefly GNAQ and GNA11. These G proteins are activated by G protein-coupled receptors (GPCRs) and relay signals to phospholipase C beta (PLCβ).

Mechanism and pathways: When a GPCR activates Gαq/11, the subunit exchanges GDP for GTP and dissociates from the Gβγ complex, stimulating PLCβ. PLCβ hydrolyzes phosphatidylinositol-4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 mobilizes Ca2+ from intracellular stores, while DAG activates protein kinase C (PKC). The resulting rise in Ca2+ and PKC activity engages downstream effectors such as the calcineurin-NFAT axis and the MAPK/ERK signaling cascade, leading to changes in gene expression, secretion, contraction, and cell proliferation. Gq/11 signaling can also influence other pathways and ion channels, contributing to diverse physiological responses.

Physiological roles: Gq11 signaling regulates vascular tone, smooth muscle function, platelet activation, and various aspects of neuronal signaling. It participates in diverse processes including secretion, growth, and coordinated responses to extracellular stimuli.

Clinical relevance: Somatic or germline alterations affecting GNAQ or GNA11 that enhance Gq signaling have been linked to certain diseases, notably uveal melanoma and vascular malformations such as blue nevi and Sturge-Weber–type lesions. These mutations often lead to constitutive activation of downstream pathways, particularly PKC and MAPK signaling, promoting cell survival and proliferation.

Therapeutic perspectives and research: Because Gq11 signaling feeds into PLCβ, PKC, and MEK/ERK axes, these nodes are explored as therapeutic targets in conditions driven by GNAQ/GNA11 mutations. Research employs modeling with constitutively active Gαq to study pathway dynamics and drug responses.