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G-Protein Coupled Receptor Signaling

Heterotrimeric G proteins are key players in transmembrane signaling, coupling a multitude of receptors to enzymes, channel proteins and other effector molecules. The heterodimeric G protein is comprised of an α subunit that has intrinsic GTPase activity and can bind to GTP. The other two subunits βγ form an undissociable complex. In the basal state the Gα subunit bound to GDP is associated with the Gβγ complex. The activation of a 7-transmembrane domain receptor by an agonist promotes the release of GDP from Gα resulting in the formation of GTP-bound Gα...

G-Protein Coupled Receptor Signaling

Pathway Summary

Heterotrimeric G proteins are key players in transmembrane signaling, coupling a multitude of receptors to enzymes, channel proteins and other effector molecules. The heterodimeric G protein is comprised of an α subunit that has intrinsic GTPase activity and can bind to GTP. The other two subunits βγ form an undissociable complex. In the basal state the Gα subunit bound to GDP is associated with the Gβγ complex. The activation of a 7-transmembrane domain receptor by an agonist promotes the release of GDP from Gα resulting in the formation of GTP-bound Gα. GTP-Gα and Gβγ dissociate and are able to modulate effector functions. The spontaneous hydrolysis of GTP to GDP can be accelerated by various effectors as well as by regulators of G protein signaling (RGS) proteins. GDP-bound Gα then reassociates with Gβγ.Several subtypes of G protein α, β and γ subunits have been described that couple combinations of activated receptors and effectors. The α subunits define the basic properties of a heterotrimeric G protein and can include the following types: Gαs, Gαi/o and Gαq/11.The Gq/G11 family of G proteins couples receptors to isoforms of phospholipase C (PLCβ). PLCβ via inositol 1, 4, 5-trisphosphate (IP3) and Diacylglycerol (DAG) activates enzymes like Calmodulin kinase (CaMK) and protein kinase C (PKC). The latter enzymes activate RAS via the inhibition of GTPases (GAP), leading to the activation of the mitogen activated protein (MAP) kinase pathway. In addition to PLCβ, the Gq family of proteins can activate proline rich tyrosine kinase (PYK2) which culminates in NF kappa B (NF-κB) activation via phosphoinositide 3 kinase (PI3K). These pathways have been implicated in several functions of the central nervous system. The ubiquitously expressed members of the Gs family couples many receptors to adenylyl cyclase activation resulting in increases in the intracellular cAMP concentration. This triggers the activation of Protein kinase A and other effectors resulting in the activation of RAF kinases. RAF kinases inturn activate the MAP kinase pathway, culminating in the activation of the cAMP response element binding (CREB) protein. The G proteins of the Gi/Go family are widely expressed and the Gi α subunits mediate receptor-dependent inhibition of various types of adenylyl cyclases. G protein-mediated signaling is thus centrally involved in diverse physiological functions such as perception of sensory information, modulation of synaptic transmission, hormone release and actions, regulation of cell contraction and migration, or cell growth and differentiation.This pathway highlights the molecular events that ensue after G proteins couple to their activated receptors. (Upgraded 07/2021)

G-Protein Coupled Receptor Signaling Genes list

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