Attenuation of GPCR Signaling Pathway

Preferred Label : Attenuation of GPCR Signaling Pathway;

NCIt related terms : Attenuation of GPCR Signaling;

Alternative definition : BIOCARTA: The G-protein coupled receptor (GPCR) family transduces extracellular signals across the plasma membrane, activating cellular responses through a variety of second messenger cascades (see PKA and PKC signaling pathways). These receptors provide rapid responses to a variety of stimuli, and are often rapidly attenuated in their signaling. Failure to attenuate GPCR signaling can have dramatic consequences. One method to attenuate GPCR signaling is by removal of the stimulus from the extracellular fluid. At the synapse, removal of neurotransmitter or peptide signaling molecules is accomplished by either reuptake or degradation. Acetylcholine is removed from synapses through degradation by the enzyme acetylcholinesterase. Inhibition of acetylcholinesterase results in prolonged signaling at the neuromuscular junction, and uncontrollable spasms in humans caused by nerve gas or in insects by some insecticides. Inhibition of acetylcholinesterase is also used therapeutically to treat Alzheimer's disease, compensating for the loss of cholinergic neurons. Transporters for serotonin, dopamine, GABA and noradrenaline remove these neurotransmitters from the synapse to terminate signaling. Antidepressants such as Prozac inhibit reuptake of serotonin and many drugs of abuse such as cocaine act by blocking reuptake of dopamine or adrenaline. Reuptake not only terminates signaling, but can also conserve neurotransmitter through recycling back into the presynaptic cell. The next step in the attenuation of GPCR signaling is receptor desensitization, in which receptors are modified to no longer transduce a signal even if the stimulus is still present. Desensitization of GPCRs occurs through protein kinases that phosphorylate the GPCR to turn off signaling. Downstream protein kinases such as PKA and PKC turned on by GPCR signaling can phosphorylate the activated GPCR and other GPCRs to prevent further signaling. G-protein receptor kinases (GRKs) are a family of kinases that specifically phosphorylate only agonist-occupied GPCRs. GRKs attenuate GPCR signaling in concert with arrestins, proteins that bind GRK-phosphorylated GPCRs to disrupt interaction with G-protein and to terminate signaling. Reducing the number of receptor expressed on the cell surface can also attenuate receptor signaling. Many GPCRs are removed from the cell surface by receptor-mediated endocytosis when they are activated. Endocytosis of activated GPCRs appears to be stimulated by GRKs and arrestins. Once internalized, receptors can either be degraded in lysosomes or they can be recycled back to the cell surface. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_agpcrPathway;

Details

Origin ID

C38974;

UMLS CUI

C1516087;

Semantic type(s)
- Molecular Function [UMLS semantic type]
has_gene_product_element
- Beta-Arrestin-1 [NCIt concept]
- Beta-Arrestin-2 [NCIt concept]
- G Protein-Coupled Receptor Kinase 4 [NCIt concept]
- Guanine Nucleotide-Binding Protein G(s) Subunit Alpha Isoforms Short [NCIt concept]
- Guanine Nucleotide-Binding Protein G(s) Subunit Alpha Isoforms XLas [NCIt concept]
- Protein Kinase C Alpha Type [NCIt concept]
- cAMP-Dependent Protein Kinase Catalytic Subunit Alpha [NCIt concept]
- cAMP-Dependent Protein Kinase Catalytic Subunit Beta [NCIt concept]
- cAMP-Dependent Protein Kinase Catalytic Subunit Gamma [NCIt concept]
- cAMP-Dependent Protein Kinase Type I-Alpha Regulatory Subunit [NCIt concept]
- cAMP-Dependent Protein Kinase Type II-Alpha Regulatory Subunit [NCIt concept]
pathway_has_gene_element
- ARRB1 wt Allele [NCIt concept]
- ARRB2 wt Allele [NCIt concept]
- GNAS wt Allele [NCIt concept]
- GRK4 wt Allele [NCIt concept]
- PRKACA wt Allele [NCIt concept]
- PRKACB wt Allele [NCIt concept]
- PRKACG wt Allele [NCIt concept]
- PRKAR1A wt Allele [NCIt concept]
- PRKAR2A wt Allele [NCIt concept]
- PRKCA wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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