PubMed:7559596 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/7559596","sourcedb":"PubMed","sourceid":"7559596","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/7559596","text":"Role of phosphorylation in agonist-promoted beta 2-adrenergic receptor sequestration. Rescue of a sequestration-defective mutant receptor by beta ARK1.\nThe beta 2-adrenergic receptor (beta 2AR) belongs to the large family of G protein-coupled receptors. Mutation of tyrosine residue 326 to an alanine resulted in a beta 2AR mutant (beta 2AR-Y326A) that was defective in its ability to sequester and was less well coupled to adenylyl cyclase than the wild-type beta 2AR. However, this mutant receptor not only desensitized in response to agonist stimulation but down-regulated normally. In an attempt to understand the basis for the properties of this mutant, we have examined the ability of this regulation-defective mutant to undergo agonist-mediated phosphorylation. When expressed in 293 cells, the maximal response for phosphorylation of the beta 2AR-Y326A mutant was impaired by 75%. Further characterization of this phosphorylation, using either forskolin stimulation or phosphorylation site-deficient beta 2AR-Y326A mutants, demonstrated that the beta 2AR-Y326A mutant can be phosphorylated by cAMP-dependent protein kinase (PKA) but does not serve as a substrate for the beta-adrenergic receptor kinase 1 (beta ARK1). However, overexpression of beta ARK1 led to the agonist-dependent phosphorylation of the beta 2AR-Y326A mutant and rescue of its sequestration. beta ARK1-mediated rescue of beta 2AR-Y326A sequestration could be prevented by mutating putative beta ARK phosphorylation sites, but not PKA phosphorylation sites. In addition, both sequestration and phosphorylation of the wild-type beta 2AR could be attenuated by overexpressing a dominant-negative mutant of beta ARK1 (C20 beta ARK1-K220M). These findings implicate a role for beta ARK1-mediated phosphorylation in facilitating wild-type beta 2AR sequestration.","tracks":[{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":85},"obj":"Sentence"},{"id":"T2","span":{"begin":86,"end":151},"obj":"Sentence"},{"id":"T3","span":{"begin":152,"end":253},"obj":"Sentence"},{"id":"T4","span":{"begin":254,"end":469},"obj":"Sentence"},{"id":"T5","span":{"begin":470,"end":585},"obj":"Sentence"},{"id":"T6","span":{"begin":586,"end":768},"obj":"Sentence"},{"id":"T7","span":{"begin":769,"end":888},"obj":"Sentence"},{"id":"T8","span":{"begin":889,"end":1225},"obj":"Sentence"},{"id":"T9","span":{"begin":1226,"end":1534},"obj":"Sentence"},{"id":"T10","span":{"begin":1535,"end":1713},"obj":"Sentence"},{"id":"T11","span":{"begin":1714,"end":1834},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":85},"obj":"Sentence"},{"id":"T2","span":{"begin":86,"end":151},"obj":"Sentence"},{"id":"T3","span":{"begin":152,"end":253},"obj":"Sentence"},{"id":"T4","span":{"begin":254,"end":469},"obj":"Sentence"},{"id":"T5","span":{"begin":470,"end":585},"obj":"Sentence"},{"id":"T6","span":{"begin":586,"end":768},"obj":"Sentence"},{"id":"T7","span":{"begin":769,"end":888},"obj":"Sentence"},{"id":"T8","span":{"begin":889,"end":1225},"obj":"Sentence"},{"id":"T9","span":{"begin":1226,"end":1534},"obj":"Sentence"},{"id":"T10","span":{"begin":1535,"end":1713},"obj":"Sentence"},{"id":"T11","span":{"begin":1714,"end":1834},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"},{"subj":"T10","pred":"source","obj":"sentences"},{"subj":"T11","pred":"source","obj":"sentences"},{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"},{"subj":"T10","pred":"source","obj":"sentences"},{"subj":"T11","pred":"source","obj":"sentences"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"sentences","color":"#93caec","default":true}]}]}}