http://purl.uniprot.org/citations/16461467 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/16461467 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/16461467 | http://www.w3.org/2000/01/rdf-schema#comment | "The insulin-regulated glucose transporter GLUT4 is a key modulator of whole body glucose homeostasis, and its selective loss in adipose tissue or skeletal muscle causes insulin resistance and diabetes. Here we report an RNA interference-based screen of protein kinases expressed in adipocytes and identify four negative regulators of insulin-responsive glucose transport: the protein kinases PCTAIRE-1 (PCTK1), PFTAIRE-1 (PFTK1), IkappaB kinase alpha, and MAP4K4/NIK. Integrin-linked protein kinase was identified as a positive regulator of this process. We characterized one of these hits, MAP4K4/NIK, and found that it is unique among mitogen-activated protein (MAP) kinases expressed in cultured adipocytes in attenuating hexose transport. Remarkably, MAP4K4/NIK suppresses expression of the adipogenic transcription factors C/EBPalpha, C/EBPbeta, and PPARgamma and of GLUT4 itself in these cells. RNA interference-mediated depletion of MAP4K4/NIK early in differentiation enhances adipogenesis and triglyceride deposition, and even in fully differentiated adipocytes its loss up-regulates GLUT4. Conversely, conditions that inhibit adipogenesis such as TNF-alpha treatment or depletion of PPARgamma markedly up-regulate MAP4K4/NIK expression in cultured adipocytes. Furthermore, TNF-alpha signaling to down-regulate GLUT4 is impaired in the absence of MAP4K4/NIK, indicating that MAP4K4 expression is required for optimal TNF-alpha action. These results reveal a MAP4K4/NIK-dependent signaling pathway that potently inhibits PPARgamma-responsive gene expression, adipogenesis, and insulin-stimulated glucose transport."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0507660103"xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0507660103"xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Czech M.P."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Czech M.P."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Tang X."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Tang X."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Powelka A.M."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Powelka A.M."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Chakladar A."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Chakladar A."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Guilherme A."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Guilherme A."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Konda S."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Konda S."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Nicoloro S.M."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Nicoloro S.M."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Straubhaar J."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Straubhaar J."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Virbasius J.V."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/author | "Virbasius J.V."xsd:string |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
http://purl.uniprot.org/citations/16461467 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |