Matches in SemOpenAlex for { <https://semopenalex.org/work/W2108031156> ?p ?o ?g. }
- W2108031156 endingPage "4744" @default.
- W2108031156 startingPage "4733" @default.
- W2108031156 abstract "The Ras-Raf-MAPK cascade is a key growth-signaling pathway and its uncontrolled activation results in cell transformation. Although the general features of the signal transmission along the cascade are reasonably defined, the mechanisms underlying Raf activation remain incompletely understood. Here, we show that Raf-1 dephosphorylation, primarily at epidermal growth factor (EGF)-induced sites, abolishes Raf-1 kinase activity. Using mass spectrometry, we identified five novel in vivo Raf-1 phosphorylation sites, one of which, S471, is located in subdomain VIB of Raf-1 kinase domain. Mutational analyses demonstrated that Raf-1 S471 is critical for Raf-1 kinase activity and for its interaction with mitogen-activated protein kinase kinase (MEK). Similarly, mutation of the corresponding B-Raf site, S578, resulted in an inactive kinase, suggesting that the same Raf-1 and B-Raf phosphorylation is needed for Raf kinase activation. Importantly, the naturally occurring, cancer-associated B-Raf activating mutation V599E suppressed the S578A mutation, suggesting that introducing a charged residue at this region eliminates the need for an activating phosphorylation. Our results demonstrate an essential role of specific EGF-induced Raf-1 phosphorylation sites in Raf-1 activation, identify Raf-1 S471 as a novel phosphorylation site critical for Raf-1 and B-Raf kinase activities, and point to the possibility that the V599E mutation activates B-Raf by mimicking a phosphorylation at the S578 site." @default.
- W2108031156 created "2016-06-24" @default.
- W2108031156 creator A5000304513 @default.
- W2108031156 creator A5000482163 @default.
- W2108031156 creator A5008594043 @default.
- W2108031156 creator A5014296728 @default.
- W2108031156 creator A5015263516 @default.
- W2108031156 creator A5022083751 @default.
- W2108031156 creator A5031714701 @default.
- W2108031156 creator A5034967177 @default.
- W2108031156 creator A5035302490 @default.
- W2108031156 creator A5043860726 @default.
- W2108031156 date "2005-10-01" @default.
- W2108031156 modified "2023-09-27" @default.
- W2108031156 title "Identification of Raf-1 S471 as a Novel Phosphorylation Site Critical for Raf-1 and B-Raf Kinase Activities and for MEK Binding" @default.
- W2108031156 cites W1505363336 @default.
- W2108031156 cites W1528493806 @default.
- W2108031156 cites W1555549645 @default.
- W2108031156 cites W1587753447 @default.
- W2108031156 cites W1666849257 @default.
- W2108031156 cites W1675086682 @default.
- W2108031156 cites W1875580551 @default.
- W2108031156 cites W1964941838 @default.
- W2108031156 cites W1965638587 @default.
- W2108031156 cites W1968142651 @default.
- W2108031156 cites W1969047667 @default.
- W2108031156 cites W1971977518 @default.
- W2108031156 cites W1983603860 @default.
- W2108031156 cites W198944900 @default.
- W2108031156 cites W1996160829 @default.
- W2108031156 cites W1996405087 @default.
- W2108031156 cites W2001895687 @default.
- W2108031156 cites W2004569739 @default.
- W2108031156 cites W2006902704 @default.
- W2108031156 cites W2007537308 @default.
- W2108031156 cites W2017461976 @default.
- W2108031156 cites W2019661351 @default.
- W2108031156 cites W2026894807 @default.
- W2108031156 cites W2030383157 @default.
- W2108031156 cites W2035936653 @default.
- W2108031156 cites W2043775652 @default.
- W2108031156 cites W2048168473 @default.
- W2108031156 cites W2049171090 @default.
- W2108031156 cites W2054292493 @default.
- W2108031156 cites W2061203237 @default.
- W2108031156 cites W2066784934 @default.
- W2108031156 cites W2074089133 @default.
- W2108031156 cites W2074571373 @default.
- W2108031156 cites W2079496856 @default.
- W2108031156 cites W2087128490 @default.
- W2108031156 cites W2090380700 @default.
- W2108031156 cites W2105086235 @default.
- W2108031156 cites W2107168679 @default.
- W2108031156 cites W2118033606 @default.
- W2108031156 cites W2122228538 @default.
- W2108031156 cites W2124662474 @default.
- W2108031156 cites W2144785546 @default.
- W2108031156 cites W2149847890 @default.
- W2108031156 cites W2163188200 @default.
- W2108031156 cites W2163908632 @default.
- W2108031156 cites W2171569176 @default.
- W2108031156 cites W2323074787 @default.
- W2108031156 cites W2323731973 @default.
- W2108031156 cites W2411534571 @default.
- W2108031156 cites W4231883944 @default.
- W2108031156 cites W4295216797 @default.
- W2108031156 doi "https://doi.org/10.1091/mbc.e05-02-0090" @default.
- W2108031156 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1237079" @default.
- W2108031156 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16093354" @default.
- W2108031156 hasPublicationYear "2005" @default.
- W2108031156 type Work @default.
- W2108031156 sameAs 2108031156 @default.
- W2108031156 citedByCount "36" @default.
- W2108031156 countsByYear W21080311562012 @default.
- W2108031156 countsByYear W21080311562013 @default.
- W2108031156 countsByYear W21080311562014 @default.
- W2108031156 countsByYear W21080311562015 @default.
- W2108031156 countsByYear W21080311562016 @default.
- W2108031156 countsByYear W21080311562017 @default.
- W2108031156 countsByYear W21080311562018 @default.
- W2108031156 countsByYear W21080311562019 @default.
- W2108031156 countsByYear W21080311562022 @default.
- W2108031156 crossrefType "journal-article" @default.
- W2108031156 hasAuthorship W2108031156A5000304513 @default.
- W2108031156 hasAuthorship W2108031156A5000482163 @default.
- W2108031156 hasAuthorship W2108031156A5008594043 @default.
- W2108031156 hasAuthorship W2108031156A5014296728 @default.
- W2108031156 hasAuthorship W2108031156A5015263516 @default.
- W2108031156 hasAuthorship W2108031156A5022083751 @default.
- W2108031156 hasAuthorship W2108031156A5031714701 @default.
- W2108031156 hasAuthorship W2108031156A5034967177 @default.
- W2108031156 hasAuthorship W2108031156A5035302490 @default.
- W2108031156 hasAuthorship W2108031156A5043860726 @default.
- W2108031156 hasBestOaLocation W21080311562 @default.
- W2108031156 hasConcept C104551158 @default.
- W2108031156 hasConcept C11960822 @default.
- W2108031156 hasConcept C124160383 @default.
- W2108031156 hasConcept C137361374 @default.