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{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/8288570","sourcedb":"PubMed","sourceid":"8288570","source_url":"https://www.ncbi.nlm.nih.gov/pubmed/8288570","text":"Inhibition of thrombin receptor signaling by a G-protein coupled receptor kinase. Functional specificity among G-protein coupled receptor kinases.\nThe thrombin receptor, a member of the seven membrane-spanning superfamily of G-protein coupled receptors, is activated by an irreversible proteolytic mechanism, but signaling by activated thrombin receptors shuts off soon after receptor activation. This shut-off mechanism is thought to be required for concentration-dependent responses to thrombin and an important determinant of the cell's sensitivity to thrombin. We report that the thrombin receptor is rapidly phosphorylated upon activation, consistent with the action of a G-protein-coupled receptor kinase. Moreover, the G-protein coupled receptor kinase BARK2 (beta-adrenergic receptor kinase 2) blocked signaling by thrombin receptors coexpressed in Xenopus oocytes. In this system, rhodopsin kinase was inactive and BARK1 was markedly less effective than BARK2. Thrombin receptor mutants which lacked potential serine and threonine phosphorylation sites in the receptor's cytoplasmic tail were insensitive to inhibition by exogenous BARK2 but did confer concentration-dependent responses to thrombin. Our studies demonstrate that a G-protein coupled receptor kinase can shut off thrombin receptor signaling but that additional mechanism(s) for terminating signaling exist. These studies also reveal functional specificity among G-protein coupled receptor kinases in a novel in vivo reconstitution system and show that heterologous expression of these kinases can be used to manipulate cellular responsiveness.","tracks":[{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":81},"obj":"Sentence"},{"id":"T2","span":{"begin":82,"end":146},"obj":"Sentence"},{"id":"T3","span":{"begin":147,"end":396},"obj":"Sentence"},{"id":"T4","span":{"begin":397,"end":564},"obj":"Sentence"},{"id":"T5","span":{"begin":565,"end":711},"obj":"Sentence"},{"id":"T6","span":{"begin":712,"end":873},"obj":"Sentence"},{"id":"T7","span":{"begin":874,"end":969},"obj":"Sentence"},{"id":"T8","span":{"begin":970,"end":1208},"obj":"Sentence"},{"id":"T9","span":{"begin":1209,"end":1380},"obj":"Sentence"},{"id":"T10","span":{"begin":1381,"end":1617},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":81},"obj":"Sentence"},{"id":"T2","span":{"begin":82,"end":146},"obj":"Sentence"},{"id":"T3","span":{"begin":147,"end":396},"obj":"Sentence"},{"id":"T4","span":{"begin":397,"end":564},"obj":"Sentence"},{"id":"T5","span":{"begin":565,"end":711},"obj":"Sentence"},{"id":"T6","span":{"begin":712,"end":873},"obj":"Sentence"},{"id":"T7","span":{"begin":874,"end":969},"obj":"Sentence"},{"id":"T8","span":{"begin":970,"end":1208},"obj":"Sentence"},{"id":"T9","span":{"begin":1209,"end":1380},"obj":"Sentence"},{"id":"T10","span":{"begin":1381,"end":1617},"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":"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"}]},{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":857,"end":864},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"262014"},{"id":"A2","pred":"db_id","subj":"T1","obj":"8353"},{"subj":"T1","pred":"source","obj":"NCBITAXON"}]},{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":192,"end":200},"obj":"Body_part"},{"id":"T4","span":{"begin":1080,"end":1091},"obj":"Body_part"},{"id":"T5","span":{"begin":1092,"end":1096},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/GO_0016020"},{"id":"A2","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000094"},{"id":"A3","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000158"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/GO_0005737"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0002415"},{"id":"A6","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_4000164"},{"subj":"T1","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T4","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T5","pred":"source","obj":"Anatomy-UBERON"}]},{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":865,"end":872},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000023"},{"subj":"T1","pred":"source","obj":"CL-cell"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"sentences","color":"#daec93","default":true},{"id":"NCBITAXON","color":"#e493ec"},{"id":"Anatomy-UBERON","color":"#93ecca"},{"id":"CL-cell","color":"#ecb093"}]}]}}