GPCR Desensitization Pathway

Source:http://linkedlifedata.com/resource/umls/id/C1517368

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umls-concept:C1517368skos:definitionNCI: 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 mlld:umls
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