| http://purl.uniprot.org/citations/23360980 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23360980 | http://www.w3.org/2000/01/rdf-schema#comment | "C-Raf is a member of the Ras-Raf-MEK-ERK mitogen-activated protein kinase (MAPK) signaling pathway that plays key roles in diverse physiological processes and is upregulated in many human cancers. C-Raf activation involves binding to Ras, increased phosphorylation and interactions with co-factors. Here, we describe a Ras-independent in vivo pathway for C-Raf activation by its downstream target MEK. Using (32)P-metabolic labeling and 2D-phosphopeptide mapping experiments, we show that MEK increases C-Raf phosphorylation by up-to 10-fold. This increase was associated with C-Raf kinase activation, matching the activity seen with growth factor stimulation. Consequently, coexpression of wildtype C-Raf and MEK was sufficient for full and constitutive activation of ERK. Notably, the ability of MEK to activate C-Raf was completely Ras independent, since mutants impaired in Ras binding that are irresponsive to growth factors or Ras were fully activated by MEK. The ability of MEK to activate C-Raf was only partially dependent on MEK kinase activity but required MEK binding to C-Raf, suggesting that the binding results in a conformational change that increases C-Raf susceptibility to phosphorylation and activation or in the stabilization of the phosphorylated-active form. These findings propose a novel Ras-independent mechanism for activating the C-Raf and the MAPK pathway without the need for mutations in the pathway. This mechanism could be of significance in pathological conditions or cancers overexpressing C-Raf and MEK or in conditions where C-Raf-MEK interaction is enhanced due to the down-regulation of RKIP and MST2."xsd:string |
| http://purl.uniprot.org/citations/23360980 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.bbamcr.2013.01.015"xsd:string |
| http://purl.uniprot.org/citations/23360980 | http://purl.uniprot.org/core/author | "Zhu J."xsd:string |
| http://purl.uniprot.org/citations/23360980 | http://purl.uniprot.org/core/author | "Rana A."xsd:string |
| http://purl.uniprot.org/citations/23360980 | http://purl.uniprot.org/core/author | "Bronisz A."xsd:string |
| http://purl.uniprot.org/citations/23360980 | http://purl.uniprot.org/core/author | "Tzivion G."xsd:string |
| http://purl.uniprot.org/citations/23360980 | http://purl.uniprot.org/core/author | "Balan V."xsd:string |
| http://purl.uniprot.org/citations/23360980 | http://purl.uniprot.org/core/author | "Leicht D.T."xsd:string |
| http://purl.uniprot.org/citations/23360980 | http://purl.uniprot.org/core/author | "Kaplun A."xsd:string |
| http://purl.uniprot.org/citations/23360980 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23360980 | http://purl.uniprot.org/core/name | "Biochim Biophys Acta"xsd:string |
| http://purl.uniprot.org/citations/23360980 | http://purl.uniprot.org/core/pages | "976-986"xsd:string |
| http://purl.uniprot.org/citations/23360980 | http://purl.uniprot.org/core/title | "MEK-1 activates C-Raf through a Ras-independent mechanism."xsd:string |
| http://purl.uniprot.org/citations/23360980 | http://purl.uniprot.org/core/volume | "1833"xsd:string |
| http://purl.uniprot.org/citations/23360980 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23360980 |
| http://purl.uniprot.org/citations/23360980 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23360980 |
| http://purl.uniprot.org/uniprot/#_P10398-mappedCitation-23360980 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23360980 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z4L5-mappedCitation-23360980 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23360980 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z559-mappedCitation-23360980 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23360980 |
| http://purl.uniprot.org/uniprot/#_B4DFY5-mappedCitation-23360980 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23360980 |
| http://purl.uniprot.org/uniprot/#_A4QPA9-mappedCitation-23360980 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23360980 |
| http://purl.uniprot.org/uniprot/#_B4E1N6-mappedCitation-23360980 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23360980 |
| http://purl.uniprot.org/uniprot/#_B4E0X2-mappedCitation-23360980 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23360980 |
| http://purl.uniprot.org/uniprot/#_L7RRS6-mappedCitation-23360980 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23360980 |