| http://purl.uniprot.org/citations/10712905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/10712905 | http://www.w3.org/2000/01/rdf-schema#comment | "Activation of the protein kinase Raf-1 is a complex process involving association with the GTP-bound form of Ras (Ras-GTP), membrane translocation and both serine/threonine and tyrosine phosphorylation (reviewed in [1]). We have reported previously that p21-activated kinase 3 (Pak3) upregulates Raf-1 through direct phosphorylation on Ser338 [2]. Here, we investigated the origin of the signal for Pak-mediated Raf-1 activation by examining the role of the small GTPase Cdc42, Rac and Ras, and of phosphatidylinositol (PI) 3-kinase. Pak3 acted synergistically with either Cdc42V12 or Rac1V12 to stimulate the activities of Raf-1, Raf-CX, a membrane-localized Raf-1 mutant, and Raf-1 mutants defective in Ras binding. Raf-1 mutants defective in Ras binding were also readily activated by RasV12. This indirect activation of Raf-1 by Ras was blocked by a dominant-negative mutant of Pak, implicating an alternative Ras effector pathway in Pak-mediated Raf-1 activation. Subsequently, we show that Pak-mediated Raf-1 activation is upregulated by both RasV12C40, a selective activator of PI 3-kinase, and p110-CX, a constitutively active PI 3-kinase. In addition, p85Delta, a mutant of the PI 3-kinase regulatory subunit, inhibited the stimulated activity of Raf-1. Pharmacological inhibitors of PI 3-kinase also blocked both activation and Ser338 phosphorylation of Raf-1 induced by epidermal growth factor (EGF). Thus, Raf-1 activation by Ras is achieved through a combination of both physical interaction and indirect mechanisms involving the activation of a second Ras effector, PI 3-kinase, which directs Pak-mediated regulatory phosphorylation of Raf-1."xsd:string |
| http://purl.uniprot.org/citations/10712905 | http://purl.org/dc/terms/identifier | "doi:10.1016/s0960-9822(00)00359-6"xsd:string |
| http://purl.uniprot.org/citations/10712905 | http://purl.uniprot.org/core/author | "Sun H."xsd:string |
| http://purl.uniprot.org/citations/10712905 | http://purl.uniprot.org/core/author | "Marshall M.S."xsd:string |
| http://purl.uniprot.org/citations/10712905 | http://purl.uniprot.org/core/author | "King A.J."xsd:string |
| http://purl.uniprot.org/citations/10712905 | http://purl.uniprot.org/core/author | "Diaz H.B."xsd:string |
| http://purl.uniprot.org/citations/10712905 | http://purl.uniprot.org/core/date | "2000"xsd:gYear |
| http://purl.uniprot.org/citations/10712905 | http://purl.uniprot.org/core/name | "Curr Biol"xsd:string |
| http://purl.uniprot.org/citations/10712905 | http://purl.uniprot.org/core/pages | "281-284"xsd:string |
| http://purl.uniprot.org/citations/10712905 | http://purl.uniprot.org/core/title | "Regulation of the protein kinase Raf-1 by oncogenic Ras through phosphatidylinositol 3-kinase, Cdc42/Rac and Pak."xsd:string |
| http://purl.uniprot.org/citations/10712905 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/10712905 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/10712905 |
| http://purl.uniprot.org/citations/10712905 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/10712905 |
| http://purl.uniprot.org/uniprot/#_P10398-mappedCitation-10712905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10712905 |
| http://purl.uniprot.org/uniprot/#_Q13554-mappedCitation-10712905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10712905 |
| http://purl.uniprot.org/uniprot/#_Q13555-mappedCitation-10712905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10712905 |
| http://purl.uniprot.org/uniprot/#_Q13557-mappedCitation-10712905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10712905 |
| http://purl.uniprot.org/uniprot/#_P15056-mappedCitation-10712905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10712905 |
| http://purl.uniprot.org/uniprot/#_P27448-mappedCitation-10712905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10712905 |
| http://purl.uniprot.org/uniprot/#_P31946-mappedCitation-10712905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10712905 |
| http://purl.uniprot.org/uniprot/#_O60674-mappedCitation-10712905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10712905 |
| http://purl.uniprot.org/uniprot/#_P01111-mappedCitation-10712905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10712905 |
| http://purl.uniprot.org/uniprot/#_P01112-mappedCitation-10712905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10712905 |
| http://purl.uniprot.org/uniprot/#_P01116-mappedCitation-10712905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10712905 |