Preferred Label : GPCR Desensitization Pathway;
NCIt related terms : beta-arrestins in GPCR Desensitization;
Alternative definition : BIOCARTA: Homologous desensitization of GPCRs results from the binding of b-arrestins
(b-arr) to agonist -occupied receptors following phosphorylation of the receptor by
GRKs. b-arrestin binding sterically precludes coupling between the receptor and heterotrimeric
G proteins, leading to termination of signaling by G proteins effectors. Receptor-bound
b-arrestins also act as adapter proteins, binding to components of the clathrin endocytic
machinery including clathrin, b2-adaptin (AP-2). Receptor sequestration reflects the
dynamin (Dyn)-dependent endocytosis of GPCRs via clathrin-coated pits. Once internalized,
GPCRs exhibit two distinct patterns of b-arrestin interaction. Class A GPCRs, for
example the b2 adrenergic receptor, rapidly dissociate from b-arrestin upon internalization.
These receptors are trafficked to an acidified endosomal compartment, wherein the
ligand is dissociated and the receptor dephosphorylated by a GPCR-specific protein
phosphatase PP2A isoform, and are subsequently recycled to the plasma membrane. Class
B receptors, for example the angiotensin II AT1a receptor, form stable receptor-b-arrestin
complexes. These receptors accumulate in endocytic vesicles and are either targeted
for degradation or slowly recycled to the membrane via as yet poorly defined routes.
(This definition may be outdated - see the DesignNote.);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Definition might be outdated or inaccurate.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_bArrestinPathway;
Origin ID : C39000;
UMLS CUI : C1517368;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
