| http://purl.uniprot.org/citations/25409143 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25409143 | http://www.w3.org/2000/01/rdf-schema#comment | "Obesity-linked insulin resistance is a major precursor to the development of type 2 diabetes. Previous work has shown that phosphorylation of PPARγ (peroxisome proliferator-activated receptor γ) at serine 273 by cyclin-dependent kinase 5 (Cdk5) stimulates diabetogenic gene expression in adipose tissues. Inhibition of this modification is a key therapeutic mechanism for anti-diabetic drugs that bind PPARγ, such as the thiazolidinediones and PPARγ partial agonists or non-agonists. For a better understanding of the importance of this obesity-linked PPARγ phosphorylation, we created mice that ablated Cdk5 specifically in adipose tissues. These mice have both a paradoxical increase in PPARγ phosphorylation at serine 273 and worsened insulin resistance. Unbiased proteomic studies show that extracellular signal-regulated kinase (ERK) kinases are activated in these knockout animals. Here we show that ERK directly phosphorylates serine 273 of PPARγ in a robust manner and that Cdk5 suppresses ERKs through direct action on a novel site in MAP kinase/ERK kinase (MEK). Importantly, pharmacological inhibition of MEK and ERK markedly improves insulin resistance in both obese wild-type and ob/ob mice, and also completely reverses the deleterious effects of the Cdk5 ablation. These data show that an ERK/Cdk5 axis controls PPARγ function and suggest that MEK/ERK inhibitors may hold promise for the treatment of type 2 diabetes."xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature13887"xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://purl.uniprot.org/core/author | "Gygi S.P."xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://purl.uniprot.org/core/author | "Spiegelman B.M."xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://purl.uniprot.org/core/author | "Shulman G.I."xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://purl.uniprot.org/core/author | "Jurczak M.J."xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://purl.uniprot.org/core/author | "McAllister F.E."xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://purl.uniprot.org/core/author | "Banks A.S."xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://purl.uniprot.org/core/author | "Laznik-Bogoslavski D."xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://purl.uniprot.org/core/author | "Camporez J.P."xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://purl.uniprot.org/core/author | "Zushin P.J."xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25409143 | http://purl.uniprot.org/core/name | "Nature"xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://purl.uniprot.org/core/pages | "391-395"xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://purl.uniprot.org/core/title | "An ERK/Cdk5 axis controls the diabetogenic actions of PPARgamma."xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://purl.uniprot.org/core/volume | "517"xsd:string |
| http://purl.uniprot.org/citations/25409143 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25409143 |
| http://purl.uniprot.org/citations/25409143 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25409143 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JDL3-mappedCitation-25409143 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25409143 |
| http://purl.uniprot.org/uniprot/#_A0A0N4SV67-mappedCitation-25409143 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25409143 |
| http://purl.uniprot.org/uniprot/#_A0A0N4SVF8-mappedCitation-25409143 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25409143 |
| http://purl.uniprot.org/uniprot/#_A0A1C9CJK6-mappedCitation-25409143 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25409143 |
| http://purl.uniprot.org/uniprot/#_A0N0C8-mappedCitation-25409143 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25409143 |
| http://purl.uniprot.org/uniprot/#_A0N0D0-mappedCitation-25409143 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25409143 |