| http://purl.uniprot.org/citations/21041952 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21041952 | http://www.w3.org/2000/01/rdf-schema#comment | "Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, unique facial features, and congenital heart disease. About 10%-15% of individuals with NS have mutations in son of sevenless 1 (SOS1), which encodes a RAS and RAC guanine nucleotide exchange factor (GEF). To understand the role of SOS1 in the pathogenesis of NS, we generated mice with the NS-associated Sos1E846K gain-of-function mutation. Both heterozygous and homozygous mutant mice showed many NS-associated pheno-types, including growth delay, distinctive facial dysmorphia, hematologic abnormalities, and cardiac defects. We found that the Ras/MAPK pathway as well as Rac and Stat3 were activated in the mutant hearts. These data provide in vivo molecular and cellular evidence that Sos1 is a GEF for Rac under physiological conditions and suggest that Rac and Stat3 activation might contribute to NS phenotypes. Furthermore, prenatal administration of a MEK inhibitor ameliorated the embryonic lethality, cardiac defects, and NS features of the homozygous mutant mice, demonstrating that this signaling pathway might represent a promising therapeutic target for NS."xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci43910"xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/author | "Araki T."xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/author | "Kucherlapati R."xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/author | "Roberts A."xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/author | "Yuan T."xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/author | "Seidman J.G."xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/author | "Wakimoto H."xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/author | "Bronson R."xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/author | "Chen P.C."xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/author | "Conner D."xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/author | "Seidman C."xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/author | "Neel B."xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/pages | "4353-4365"xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/title | "Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndrome-associated Sos1 mutation."xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://purl.uniprot.org/core/volume | "120"xsd:string |
| http://purl.uniprot.org/citations/21041952 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21041952 |
| http://purl.uniprot.org/citations/21041952 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21041952 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JGF4-mappedCitation-21041952 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21041952 |
| http://purl.uniprot.org/uniprot/#_A0A087WPS3-mappedCitation-21041952 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21041952 |
| http://purl.uniprot.org/uniprot/#_D3Z783-mappedCitation-21041952 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21041952 |
| http://purl.uniprot.org/uniprot/#_A0A087WPJ5-mappedCitation-21041952 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21041952 |