| http://purl.uniprot.org/citations/12167719 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12167719 | http://www.w3.org/2000/01/rdf-schema#comment | "beta-Arrestin-1 mediates agonist-dependent desensitization and internalization of G protein-coupled receptors (GPCRs) and is also essential for GPCR mitogenic signaling. In addition, insulin-like growth factor I receptor (IGF-IR) endocytosis is facilitated by beta-arrestin-1, and internalization is necessary for IGF-I-stimulated mitogen-activated protein (MAP) kinase activation. Here, we report that treatment of cells for 12 h with insulin (100 ng/ml) induces an approximately 50% decrease in cellular beta-arrestin-1 content due to ubiquitination of beta-arrestin-1 and proteosome-mediated degradation. This insulin-induced decrease in beta-arrestin-1 content was blocked by inhibition of phosphatidylinositol-3 kinase (PI-3 kinase) and MEK with wortmannin and PD98059, respectively. We also found a marked decrease in the association of beta-arrestin-1 with the IGF-IR and a 55% inhibition of IGF-I-stimulated MAP kinase phosphorylation. In insulin-treated, beta-arrestin-1-downregulated cells, there was complete inhibition of lysophosphatidic acid (LPA) or isoproterenol (ISO)-stimulated MAP kinase phosphorylation. This was associated with a decrease in beta-arrestin-1 association with the beta2-AR as well as a decrease in beta-arrestin-1-Src and Src-beta2-AR association. Ectopic expression of wild-type beta-arrestin-1 in insulin-treated cells in which endogenous beta-arrestin-1 had been downregulated rescued IGF-I- and LPA-stimulated MAP kinase phosphorylation. In conclusion, we found the following. (i) Chronic insulin treatment leads to enhanced beta-arrestin-1 degradation. (ii) This downregulation of endogenous beta-arrestin-1 is associated with decreased IGF-I-, LPA-, and ISO-mediated MAP kinase signaling, which can be rescued by ectopic expression of wild-type beta-arrestin-1. (iii) Finally, these results describe a novel mechanism for heterologous desensitization, whereby insulin treatment can impair GPCR signaling, and highlight the importance of beta-arrestin-1 as a target molecule for this desensitization mechanism."xsd:string |
| http://purl.uniprot.org/citations/12167719 | http://purl.org/dc/terms/identifier | "doi:10.1128/mcb.22.17.6272-6285.2002"xsd:string |
| http://purl.uniprot.org/citations/12167719 | http://purl.uniprot.org/core/author | "Imamura T."xsd:string |
| http://purl.uniprot.org/citations/12167719 | http://purl.uniprot.org/core/author | "Dalle S."xsd:string |
| http://purl.uniprot.org/citations/12167719 | http://purl.uniprot.org/core/author | "Rose D.W."xsd:string |
| http://purl.uniprot.org/citations/12167719 | http://purl.uniprot.org/core/author | "Olefsky J.M."xsd:string |
| http://purl.uniprot.org/citations/12167719 | http://purl.uniprot.org/core/author | "Ugi S."xsd:string |
| http://purl.uniprot.org/citations/12167719 | http://purl.uniprot.org/core/author | "Worrall D.S."xsd:string |
| http://purl.uniprot.org/citations/12167719 | http://purl.uniprot.org/core/author | "Hupfeld C.J."xsd:string |
| http://purl.uniprot.org/citations/12167719 | http://purl.uniprot.org/core/date | "2002"xsd:gYear |
| http://purl.uniprot.org/citations/12167719 | http://purl.uniprot.org/core/name | "Mol Cell Biol"xsd:string |
| http://purl.uniprot.org/citations/12167719 | http://purl.uniprot.org/core/pages | "6272-6285"xsd:string |
| http://purl.uniprot.org/citations/12167719 | http://purl.uniprot.org/core/title | "Insulin induces heterologous desensitization of G-protein-coupled receptor and insulin-like growth factor I signaling by downregulating beta-arrestin-1."xsd:string |
| http://purl.uniprot.org/citations/12167719 | http://purl.uniprot.org/core/volume | "22"xsd:string |
| http://purl.uniprot.org/citations/12167719 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/12167719 |
| http://purl.uniprot.org/citations/12167719 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/12167719 |
| http://purl.uniprot.org/uniprot/P29066#attribution-456E5983DFC2261BB3208A2816D3EAD3 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/12167719 |
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