| http://purl.uniprot.org/citations/14530258 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/14530258 | http://www.w3.org/2000/01/rdf-schema#comment | "Activation of the serine/threonine kinase c-Raf-1 requires membrane localization, phosphorylation, and oligomerization. To study these mechanisms of Raf activation more precisely, we have used a membrane-localized fusion protein, myr-Raf-GyrB, which can be activated by coumermycin-induced oligomerization in NIH3T3 transfectants. By introducing a series of point mutations into the myr-Raf-GyrB kinase domain (S338A, S338A/Y341F, Y340F/Y341F, and T491A/S494A) we can separately study the role that membrane localization, phosphorylation, and oligomerization play in the process of Raf activation. We find that phosphorylation of Ser-338 plays a critical role in Raf activation and that this requires membrane localization but not oligomerization of Raf. Mutation of Tyr-341 had a limited effect, whereas mutation of both Ser-338 and Tyr-341 resulted in a synergistic loss of Raf activation following coumermycin-induced dimerization. Importantly, we found that membrane localization and phosphorylation of Ser-338 were not sufficient to activate Raf in the absence of oligomerization. Thus, our studies suggest that three key steps are required for optimal Raf activation: recruitment to the plasma membrane by GTP-bound Ras, phosphorylation via membrane-resident kinases, and oligomerization."xsd:string |
| http://purl.uniprot.org/citations/14530258 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m309183200"xsd:string |
| http://purl.uniprot.org/citations/14530258 | http://purl.uniprot.org/core/author | "Farrar M.A."xsd:string |
| http://purl.uniprot.org/citations/14530258 | http://purl.uniprot.org/core/author | "O'Neil J.J."xsd:string |
| http://purl.uniprot.org/citations/14530258 | http://purl.uniprot.org/core/author | "Goetz C.A."xsd:string |
| http://purl.uniprot.org/citations/14530258 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/14530258 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/14530258 | http://purl.uniprot.org/core/pages | "51184-51189"xsd:string |
| http://purl.uniprot.org/citations/14530258 | http://purl.uniprot.org/core/title | "Membrane localization, oligomerization, and phosphorylation are required for optimal raf activation."xsd:string |
| http://purl.uniprot.org/citations/14530258 | http://purl.uniprot.org/core/volume | "278"xsd:string |
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| http://purl.uniprot.org/uniprot/#_Q14738-mappedCitation-14530258 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/14530258 |
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| http://purl.uniprot.org/uniprot/#_P30154-mappedCitation-14530258 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/14530258 |
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| http://purl.uniprot.org/uniprot/#_P62140-mappedCitation-14530258 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/14530258 |