Gsproteiinin

Gsproteiinin, commonly referred to as the Gs protein or the Gαs subunit, is a stimulatory component of heterotrimeric G proteins involved in transducing signals from many G protein-coupled receptors (GPCRs) to intracellular effectors. In its inactive state, Gαs is bound to GDP and associated with the Gβγ dimer at the plasma membrane. Upon receptor activation, GPCRs function as guanine nucleotide exchange factors, promoting the exchange of GDP for GTP on Gαs. Gαs–GTP then dissociates from Gβγ and activates adenylyl cyclase, increasing intracellular cyclic AMP (cAMP) levels. The rise in cAMP activates protein kinase A (PKA) and other cAMP-responsive pathways, leading to diverse cellular responses such as changes in metabolism, ion channel activity, and gene expression.

Termination of signaling occurs as Gαs hydrolyzes GTP to GDP intrinsic to the protein, re-associates with Gβγ, and reforms the inactive heterotrimer. Regulation also involves regulators of G protein signaling (RGS proteins) and receptor desensitization mechanisms.

Genetically, the Gsα subunit is encoded by the GNAS locus, which exhibits tissue-specific imprinting and produces multiple transcripts. Activating somatic mutations in GNAS can cause McCune-Albright syndrome, while inactivating or imprinting-related alterations can lead to pseudohypoparathyroidism type I. Because Gs signaling affects numerous organ systems, its dysfunction can contribute to a range of endocrine, metabolic, and developmental disorders.