http://purl.uniprot.org/citations/16725308 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/16725308 | http://www.w3.org/2000/01/rdf-schema#comment | "G-protein-coupled-receptor kinase 2 (GRK2) plays a key role in the modulation of G-protein-coupled-receptor (GPCR) signaling by both phosphorylating agonist-occupied GPCRs and by directly binding to activated Galphaq subunits, inhibiting downstream effectors activation. The GRK2/Galphaq interaction involves the N-terminal region of the kinase that displays homology to regulators of G-protein signaling (RGS) proteins. We have previously reported that upon GPCR stimulation, GRK2 can be phosphorylated by c-Src on tyrosine residues that are present in the RGS-homology (RH) region of this kinase. Here, we demonstrate that c-Src kinase activity increases the interaction between GRK2 and Galphaq. Tyrosine phosphorylation of GRK2 appears to be critically involved in the modulation of this interaction since the stimulatory effect of c-Src is not observed with a GRK2 mutant with impaired tyrosine phosphorylation (GRK2 Y13,86,92F), whereas a mutant that mimics GRK2 tyrosine phosphorylation in these residues displays an increased interaction with Galphaq. As evidence for a physiological role of this modulatory mechanism, activation of the muscarinic receptor M1, a Galphaq-coupled receptor, promotes an increase in GRK2/Galphaq co-immunoprecipitation that parallels the enhanced GRK2 phosphorylation on tyrosine residues. Moreover, c-Src activation enhances inhibition of the Galphaq/phospholipase Cbeta signaling pathway in intact cells, in a GRK2-tyrosine-phosphorylation-dependent manner. Our results suggest a feedback mechanism by which phosphorylation of GRK2 by c-Src increases both GRK2 kinase activity towards GPCRs and its specific interaction with Galphaq subunits, leading to a more rapid switch off of Galphaq-mediated signaling."xsd:string |
http://purl.uniprot.org/citations/16725308 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.cellsig.2006.03.004"xsd:string |
http://purl.uniprot.org/citations/16725308 | http://purl.uniprot.org/core/author | "Mayor F. Jr."xsd:string |
http://purl.uniprot.org/citations/16725308 | http://purl.uniprot.org/core/author | "De Blasi A."xsd:string |
http://purl.uniprot.org/citations/16725308 | http://purl.uniprot.org/core/author | "Mariggio S."xsd:string |
http://purl.uniprot.org/citations/16725308 | http://purl.uniprot.org/core/author | "Ribas C."xsd:string |
http://purl.uniprot.org/citations/16725308 | http://purl.uniprot.org/core/author | "Sarnago S."xsd:string |
http://purl.uniprot.org/citations/16725308 | http://purl.uniprot.org/core/author | "Garcia-Hoz C."xsd:string |
http://purl.uniprot.org/citations/16725308 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
http://purl.uniprot.org/citations/16725308 | http://purl.uniprot.org/core/name | "Cell Signal"xsd:string |
http://purl.uniprot.org/citations/16725308 | http://purl.uniprot.org/core/pages | "2004-2012"xsd:string |
http://purl.uniprot.org/citations/16725308 | http://purl.uniprot.org/core/title | "Tyrosine phosphorylation of G-protein-coupled-receptor kinase 2 (GRK2) by c-Src modulates its interaction with Galphaq."xsd:string |
http://purl.uniprot.org/citations/16725308 | http://purl.uniprot.org/core/volume | "18"xsd:string |
http://purl.uniprot.org/citations/16725308 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16725308 |
http://purl.uniprot.org/citations/16725308 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/16725308 |
http://purl.uniprot.org/uniprot/#_A0A0S2Z392-mappedCitation-16725308 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16725308 |
http://purl.uniprot.org/uniprot/#_A0A0S2Z3I6-mappedCitation-16725308 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16725308 |
http://purl.uniprot.org/uniprot/#_P25098-mappedCitation-16725308 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16725308 |
http://purl.uniprot.org/uniprot/#_Q59F73-mappedCitation-16725308 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16725308 |
http://purl.uniprot.org/uniprot/A0A0S2Z392 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/16725308 |
http://purl.uniprot.org/uniprot/P25098 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/16725308 |
http://purl.uniprot.org/uniprot/A0A0S2Z3I6 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/16725308 |
http://purl.uniprot.org/uniprot/Q59F73 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/16725308 |