Biol 2C Quiz 2, Spring 2017 7. Following their activation upon binding to ligand
ID: 162766 • Letter: B
Question
Biol 2C Quiz 2, Spring 2017 7. Following their activation upon binding to ligand, G protein-coupled receptors, GPCRs, in turn activate G proteins and thereby initiate a signaling cascade. Following ligand binding, GPCRs become phosphorylated by G protein receptor kinases (GRKs) which, in tum, leads to desensitization of the receptor such that continued stimulation by ligand results in a waning responsiveness of the ce Arrestins are proteins that bind to GPCRs and are involved in this desensitization. In order to understand GPCR-arrestin interactions, the B -adrenergic receptor (B2-AR, a GPCR, and its interaction with Barrestin are subjected to study. A cell line expressing the BT-AR is incubated in epinephrine, aligand for this receptor, for 5 minutes. The cells are then lysed and the BrAR is immunoprecipitated from the lysate. To determine ifB arrestin is bound to the receptor, the immunoprecipitate is examined by Western blotting using an antibody directed against Bamestin. The experiment is repeated, but this time prior to and during epinephrine addition the cells are incubated in an inhibitor that blocks BrAR phosphory by the kinase GRK2 (BARK) The data are shown below. ation Barresti min in a) How does the activation state of the receptor affect Barrestin binding? b) What information do the kinase inhibitor studies provide about Bamestin binding to the receptor?Explanation / Answer
Generally activated B2-AR activates Gs. Gs get activated when ligand epinephrine is present. Activated Gs goes through GTP hydrolysis. GTPase activity measures the GTP hydrolysis. Measurement of GTPase activity measures the initial events of signaling cascade. Addition of kinase/GRK2 leads to phosphorylation of receptor. Due to phosphorylation of receptor, Gs activation wont gets arrested completely. Addition of GRK2 and B-arrestin, results in complete arrest of Gs activation. Thus B-arrestin alone cannot affect Gs activation. B-arrestin along with kinase arrest Gs activation. This shows that B-arrestin can bind to phosphorylated receptor alone. Arrestins have been involved in desensitization through binding to phosphorylated receptor. Arrestins coupled to kinases interfere the signaling to Gs activation. Even in the presence of a ligand binding to receptor, due to desensitization of arrestins through their binding to phosphorylated receptor, cannot signal to Gs activation.
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