G-protein-coupled receptor-related signaling pathways via gene expression modulation

G-protein-coupled receptor-related signaling pathways via gene expression modulation refer to the complex intracellular processes where extracellular signals, sensed by G-protein-coupled receptors (GPCRs), are converted into nuclear responses. Upon ligand binding, GPCRs activate heterotrimeric G proteins, which trigger second messengers like cAMP, calcium ions, or diacylglycerol (StatPearls, 2023). These messengers activate protein kinases such as PKA, PKC, or MAPK that translocate to the nucleus to phosphorylate transcription factors like CREB, ELK1, or NF-kB, thereby altering the cell's transcriptome (Nature Reviews Molecular Cell Biology, 2002). This mechanism is essential for long-term physiological adaptations, including memory formation, immune cell activation, and metabolic regulation. In various diseases, these pathways are often dysregulated; for instance, overactive GPCR signaling can drive the expression of oncogenes in cancer or pro-inflammatory cytokines in autoimmune disorders (Pharmacological Reviews, 2018). While this entry describes a biological process rather than a single protein, it represents the functional outcome of many therapeutic interventions. Drugs targeting specific GPCRs, such as beta-blockers or angiotensin receptor blockers, exert their long-term clinical effects by indirectly modulating these gene expression pathways to restore homeostatic balance in the cardiovascular or nervous systems.

Other names

GPCR-mediated gene regulationG protein-coupled receptor signaling pathwayGPCR-to-nucleus signalingGPCR-induced transcriptional regulation

Modulation of G-protein-coupled receptors to activate or inhibit downstream intracellular signaling cascades (e.g., cAMP/PKA, PLC/PKC, or MAPK pathways) that ultimately regulate the activity of transcription factors and the expression of target genes.