| http://purl.uniprot.org/citations/12612072 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12612072 | http://www.w3.org/2000/01/rdf-schema#comment | "It is widely thought that the biological outcomes of Raf-1 activation are solely attributable to the activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. However, an increasing number of reports suggest that some Raf-1 functions are independent of this pathway. In this report we show that mutation of the amino-terminal 14-3-3 binding site of Raf-1 uncouples its ability to activate the MEK/ERK pathway from the induction of cell transformation and differentiation. In NIH 3T3 fibroblasts and COS-1 cells, mutation of serine 259 resulted in Raf-1 proteins which activated the MEK/ERK pathway as efficiently as v-Raf. However, in contrast to v-Raf, RafS259 mutants failed to transform. They induced morphological alterations and slightly accelerated proliferation in NIH 3T3 fibroblasts but were not tumorigenic in mice and behaved like wild-type Raf-1 in transformation assays measuring loss of contact inhibition or anchorage-independent growth. Curiously, the RafS259 mutants inhibited focus induction by an activated MEK allele, suggesting that they can hyperactivate negative-feedback pathways. In primary cultures of postmitotic chicken neuroretina cells, RafS259A was able to sustain proliferation to a level comparable to that sustained by the membrane-targeted transforming Raf-1 protein, RafCAAX. In contrast, RafS259A was only a poor inducer of neurite formation in PC12 cells in comparison to RafCAAX. Thus, RafS259 mutants genetically separate MEK/ERK activation from the ability of Raf-1 to induce transformation and differentiation. The results further suggest that RafS259 mutants inhibit signaling pathways required to promote these biological processes."xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.org/dc/terms/identifier | "doi:10.1128/mcb.23.6.1983-1993.2003"xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/author | "Dhillon A.S."xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/author | "Kolch W."xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/author | "Mischak H."xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/author | "Steen H."xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/author | "Eychene A."xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/author | "Kaiser C."xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/author | "Grindlay J."xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/author | "Shaw P.E."xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/author | "Meikle S."xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/author | "Peyssonnaux C."xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/name | "Mol Cell Biol"xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/pages | "1983-1993"xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/title | "A Raf-1 mutant that dissociates MEK/extracellular signal-regulated kinase activation from malignant transformation and differentiation but not proliferation."xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://purl.uniprot.org/core/volume | "23"xsd:string |
| http://purl.uniprot.org/citations/12612072 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/12612072 |
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| http://purl.uniprot.org/uniprot/#_Q63844-mappedCitation-12612072 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/12612072 |
| http://purl.uniprot.org/uniprot/#_Q3U2H3-mappedCitation-12612072 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/12612072 |
| http://purl.uniprot.org/uniprot/#_Q922X7-mappedCitation-12612072 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/12612072 |