| http://purl.uniprot.org/citations/22133875 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22133875 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations in the coactivator CREB-binding protein (CBP) are a major cause of the human skeletal dysplasia Rubinstein-Taybi syndrome (RTS); however, the mechanism by which these mutations affect skeletal mineralization and patterning is unknown. Here, we report the identification of 3-phosphoinositide-dependent kinase 1 (PDK1) as a key regulator of CBP activity and demonstrate that its functions map to both osteoprogenitor cells and mature osteoblasts. In osteoblasts, PDK1 activated the CREB/CBP complex, which in turn controlled runt-related transcription factor 2 (RUNX2) activation and expression of bone morphogenetic protein 2 (BMP2). These pathways also operated in vivo, as evidenced by recapitulation of RTS spectrum phenotypes with osteoblast-specific Pdk1 deletion in mice (Pdk1osx mice) and by the genetic interactions observed in mice heterozygous for both osteoblast-specific Pdk1 deletion and either Runx2 or Creb deletion. Finally, treatment of Pdk1osx and Cbp+/-embryos with BMPs in utero partially reversed their skeletal anomalies at birth. These findings illustrate the in vivo function of the PDK1-AKT-CREB/CBP pathway in bone formation and provide proof of principle for in utero growth factor supplementation as a potential therapy for skeletal dysplasias."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci59466"xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/author | "Singh A."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/author | "Kasuga M."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/author | "Lee S.K."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/author | "Yang S.H."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/author | "Brady N."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/author | "Hu D."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/author | "Noda T."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/author | "Ogawa W."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/author | "Glimcher L.H."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/author | "Shim J.H."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/author | "Rebel V.I."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/author | "Greenblatt M.B."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/author | "Drapp R."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/pages | "91-106"xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/title | "Administration of BMP2/7 in utero partially reverses Rubinstein-Taybi syndrome-like skeletal defects induced by Pdk1 or Cbp mutations in mice."xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://purl.uniprot.org/core/volume | "122"xsd:string |
| http://purl.uniprot.org/citations/22133875 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22133875 |
| http://purl.uniprot.org/citations/22133875 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22133875 |
| http://purl.uniprot.org/uniprot/#_F2Z3V6-mappedCitation-22133875 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22133875 |
| http://purl.uniprot.org/uniprot/#_A0A087WRI6-mappedCitation-22133875 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22133875 |