FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2799668898> ?p ?o ?g. }

• W2799668898 endingPage "1780" @default.
• W2799668898 startingPage "1773" @default.
• W2799668898 abstract "Abstract Mutated in approximately 30% of human cancers, Ras GTPases are the most common drivers of oncogenesis and render tumors unresponsive to many standard therapies. Despite decades of research, no drugs directly targeting Ras are currently available. We have previously characterized a small protein antagonist of K-Ras, R11.1.6, and demonstrated its direct competition with Raf for Ras binding. Here we evaluate the effects of R11.1.6 on Ras signaling and cellular proliferation in a panel of human cancer cell lines. Through lentiviral transduction, we generated cell lines that constitutively or through induction with doxycycline express R11.1.6 or a control protein YW1 and show specific binding by R11.1.6 to endogenous Ras through microscopy and co-immunoprecipitation experiments. Genetically encoded intracellular expression of this high-affinity Ras antagonist, however, fails to measurably disrupt signaling through either the MAPK or PI3K pathway. Consistently, cellular proliferation was unaffected as well. To understand this lack of signaling inhibition, we quantified the number of molecules of R11.1.6 expressed by the inducible cell lines and developed a simple mathematical model describing the competitive binding of Ras by R11.1.6 and Raf. This model supports a potential mechanism for the lack of biological effects that we observed, suggesting stoichiometric and thermodynamic barriers that should be overcome in pharmacologic efforts to directly compete with downstream effector proteins localized to membranes at very high effective concentrations. Mol Cancer Ther; 17(8); 1773–80. ©2018 AACR." @default.
• W2799668898 created "2018-05-17" @default.
• W2799668898 creator A5022296765 @default.
• W2799668898 creator A5036252189 @default.
• W2799668898 creator A5048283562 @default.
• W2799668898 creator A5089515174 @default.
• W2799668898 creator A5089724504 @default.
• W2799668898 creator A5089833949 @default.
• W2799668898 date "2018-07-31" @default.
• W2799668898 modified "2023-10-16" @default.
• W2799668898 title "A Raf-Competitive K-Ras Binder Can Fail to Functionally Antagonize Signaling" @default.
• W2799668898 cites W1585517331 @default.
• W2799668898 cites W169361905 @default.
• W2799668898 cites W1967761542 @default.
• W2799668898 cites W1984906223 @default.
• W2799668898 cites W198944900 @default.
• W2799668898 cites W1996338307 @default.
• W2799668898 cites W2010234097 @default.
• W2799668898 cites W2012479646 @default.
• W2799668898 cites W2022920832 @default.
• W2799668898 cites W2052051648 @default.
• W2799668898 cites W2052811553 @default.
• W2799668898 cites W2058511768 @default.
• W2799668898 cites W2070023258 @default.
• W2799668898 cites W2070658593 @default.
• W2799668898 cites W2075989748 @default.
• W2799668898 cites W2081990599 @default.
• W2799668898 cites W2087778160 @default.
• W2799668898 cites W2096595244 @default.
• W2799668898 cites W2098760239 @default.
• W2799668898 cites W2102099949 @default.
• W2799668898 cites W2128339707 @default.
• W2799668898 cites W2134629247 @default.
• W2799668898 cites W2143945587 @default.
• W2799668898 cites W2144265524 @default.
• W2799668898 cites W2147687412 @default.
• W2799668898 cites W2157297563 @default.
• W2799668898 cites W2159440209 @default.
• W2799668898 cites W2166077873 @default.
• W2799668898 cites W2168770561 @default.
• W2799668898 cites W2171437999 @default.
• W2799668898 cites W2233032895 @default.
• W2799668898 cites W2333950962 @default.
• W2799668898 cites W2474410556 @default.
• W2799668898 cites W2510025743 @default.
• W2799668898 cites W2548573003 @default.
• W2799668898 cites W2559953355 @default.
• W2799668898 cites W2613701746 @default.
• W2799668898 cites W2734751189 @default.
• W2799668898 doi "https://doi.org/10.1158/1535-7163.mct-17-0645" @default.
• W2799668898 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29720559" @default.
• W2799668898 hasPublicationYear "2018" @default.
• W2799668898 type Work @default.
• W2799668898 sameAs 2799668898 @default.
• W2799668898 citedByCount "8" @default.
• W2799668898 countsByYear W27996688982019 @default.
• W2799668898 countsByYear W27996688982020 @default.
• W2799668898 countsByYear W27996688982021 @default.
• W2799668898 countsByYear W27996688982022 @default.
• W2799668898 countsByYear W27996688982023 @default.
• W2799668898 crossrefType "journal-article" @default.
• W2799668898 hasAuthorship W2799668898A5022296765 @default.
• W2799668898 hasAuthorship W2799668898A5036252189 @default.
• W2799668898 hasAuthorship W2799668898A5048283562 @default.
• W2799668898 hasAuthorship W2799668898A5089515174 @default.
• W2799668898 hasAuthorship W2799668898A5089724504 @default.
• W2799668898 hasAuthorship W2799668898A5089833949 @default.
• W2799668898 hasBestOaLocation W27996688981 @default.
• W2799668898 hasConcept C121608353 @default.
• W2799668898 hasConcept C127812441 @default.
• W2799668898 hasConcept C150555746 @default.
• W2799668898 hasConcept C163181125 @default.
• W2799668898 hasConcept C207332259 @default.
• W2799668898 hasConcept C502942594 @default.
• W2799668898 hasConcept C51785407 @default.
• W2799668898 hasConcept C54355233 @default.
• W2799668898 hasConcept C55493867 @default.
• W2799668898 hasConcept C555283112 @default.
• W2799668898 hasConcept C57074206 @default.
• W2799668898 hasConcept C62112901 @default.
• W2799668898 hasConcept C62478195 @default.
• W2799668898 hasConcept C79879829 @default.
• W2799668898 hasConcept C80631254 @default.
• W2799668898 hasConcept C81885089 @default.
• W2799668898 hasConcept C86554907 @default.
• W2799668898 hasConcept C86803240 @default.
• W2799668898 hasConcept C95444343 @default.
• W2799668898 hasConcept C96232424 @default.
• W2799668898 hasConceptScore W2799668898C121608353 @default.
• W2799668898 hasConceptScore W2799668898C127812441 @default.
• W2799668898 hasConceptScore W2799668898C150555746 @default.
• W2799668898 hasConceptScore W2799668898C163181125 @default.
• W2799668898 hasConceptScore W2799668898C207332259 @default.
• W2799668898 hasConceptScore W2799668898C502942594 @default.
• W2799668898 hasConceptScore W2799668898C51785407 @default.
• W2799668898 hasConceptScore W2799668898C54355233 @default.
• W2799668898 hasConceptScore W2799668898C55493867 @default.
• W2799668898 hasConceptScore W2799668898C555283112 @default.

• next