Agonist-induced signaling, desensitization, and internalization of a phosphorylation-deficient AT1A angiotensin receptor.
作者： László Hunyady , Roger D. Smith , Bukhtiar H. Shah , J. Alberto Olivares-Reyes , Kevin J. Catt
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摘要: Abstract An analysis of the functional role a diacidic motif (Asp236-Asp237) in third intracellular loop AT1A angiotensin II (Ang II) receptor (AT1-R) revealed that substitution both amino acids with alanine (DD-AA) or asparagine (DD-NN) residues diminished Ang II-induced phosphorylation COS-7 cells. However, II-stimulated inositol phosphate production, mitogen-activated protein kinase, and AT1 desensitization internalization were not significantly impaired. Overexpression dominant negative G protein-coupled kinase 2 (GRK2)K220M decreased agonist-induced by ∼40%, but did further reduce impaired DD-AA DD-NN receptors. Inhibition C bisindolylmaleimide reduced wild-type DD mutant receptors ∼30%. The inhibitory effects GRK2K220M expression inhibition on additive for AT1-R, receptor. Agonist-induced was similar unaltered coexpression GRK2K220M. These findings demonstrate an acidic at position 236/237 AT1-R is required optimal its carboxyl-terminal tail GRKs. Furthermore, properties suggest only signaling, also internalization, are independent GRK-mediated
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