FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2024957091> ?p ?o ?g. }

• W2024957091 endingPage "1067" @default.
• W2024957091 startingPage "1058" @default.
• W2024957091 abstract "The Raf/MEK/ERK kinase cascade plays a critical role in transducing growth signals from activated cell surface receptors. Using ΔMEK1:ER, a conditionally active form of MEK1 which responds to either β-estradiol or the estrogen receptor antagonist 4 hydroxy-tamoxifen (4HT), we previously documented the ability of this dual specificity protein kinase to abrogate the cytokine-dependency of human (TF-1) and murine (FDC-P1 and FL5.12) hematopoietic cells lines. Here we demonstrate the ability of ΔMEK1:ER to activate the phosphatidylinositol 3-kinase (PI3K)/Akt/p70 ribosomal S6 kinase (p70S6K) pathway and the importance of this pathway in MEK1-mediated prevention of apoptosis. MEK1-responsive cells can be maintained long term in the presence of β-estradiol, 4HT or IL-3. Removal of hormone led to the rapid cessation of cell proliferation and the induction of apoptosis in a manner similar to cytokine deprivation of the parental cells. Stimulation of ΔMEK1:ER by 4HT resulted in ERK, PI3K, Akt and p70S6K activation. Treatment with PI3K, Akt and p70S6K inhibitors prevented MEK-responsive growth. Furthermore, the apoptotic effects of PI3K/Akt/p70S6K inhibitors could be enhanced by cotreatment with MEK inhibitors. Use of a PI3K inhibitor and a constitutively active form of Akt, [ΔAkt(Myr+)], indicated that activation of PI3K was necessary for MEK1-responsive growth and survival as activation of Akt alone was unable to compensate for the loss of PI3K activity. Cells transduced by MEK or MEK+Akt displayed different sensitivities to signal transduction inhibitors, which targeted these pathways. These results indicate a requirement for the activation of the PI3K pathway during MEK-mediated transformation of certain hematopoietic cells. These experiments provide important clues as to why the identification of mutant signaling pathways may be the Achilles heel of leukemic cell growth. Leukemia treatment targeting multiple signal transduction pathways may be more efficacious than therapy aimed at inhibiting a single pathway." @default.
• W2024957091 created "2016-06-24" @default.
• W2024957091 creator A5003308880 @default.
• W2024957091 creator A5003652463 @default.
• W2024957091 creator A5018679533 @default.
• W2024957091 creator A5030391285 @default.
• W2024957091 creator A5039157054 @default.
• W2024957091 creator A5047268135 @default.
• W2024957091 creator A5055448946 @default.
• W2024957091 creator A5059323796 @default.
• W2024957091 creator A5066385674 @default.
• W2024957091 creator A5073310914 @default.
• W2024957091 creator A5091807722 @default.
• W2024957091 date "2003-05-23" @default.
• W2024957091 modified "2023-10-15" @default.
• W2024957091 title "Requirement for the PI3K/Akt pathway in MEK1-mediated growth and prevention of apoptosis: identification of an Achilles heel in leukemia" @default.
• W2024957091 cites W133636034 @default.
• W2024957091 cites W1968092445 @default.
• W2024957091 cites W1970834072 @default.
• W2024957091 cites W1975118026 @default.
• W2024957091 cites W1975642651 @default.
• W2024957091 cites W1982920370 @default.
• W2024957091 cites W1987035130 @default.
• W2024957091 cites W1989512056 @default.
• W2024957091 cites W1994835972 @default.
• W2024957091 cites W2004530777 @default.
• W2024957091 cites W2015507268 @default.
• W2024957091 cites W2016151378 @default.
• W2024957091 cites W2024002276 @default.
• W2024957091 cites W2027847139 @default.
• W2024957091 cites W2032586424 @default.
• W2024957091 cites W2034895195 @default.
• W2024957091 cites W2036265336 @default.
• W2024957091 cites W2039558513 @default.
• W2024957091 cites W2050988292 @default.
• W2024957091 cites W2059668731 @default.
• W2024957091 cites W2059692699 @default.
• W2024957091 cites W2070387456 @default.
• W2024957091 cites W2073925779 @default.
• W2024957091 cites W2075091190 @default.
• W2024957091 cites W2079520443 @default.
• W2024957091 cites W2086025404 @default.
• W2024957091 cites W2091453309 @default.
• W2024957091 cites W2092923321 @default.
• W2024957091 cites W2170839629 @default.
• W2024957091 cites W2175994433 @default.
• W2024957091 cites W226520676 @default.
• W2024957091 cites W2312511698 @default.
• W2024957091 cites W2313576573 @default.
• W2024957091 cites W2316737344 @default.
• W2024957091 cites W2317478958 @default.
• W2024957091 cites W2320805399 @default.
• W2024957091 cites W2321226355 @default.
• W2024957091 cites W2322277401 @default.
• W2024957091 cites W2326389383 @default.
• W2024957091 cites W2326572877 @default.
• W2024957091 cites W2327387659 @default.
• W2024957091 cites W2327584915 @default.
• W2024957091 cites W2328289012 @default.
• W2024957091 cites W2330527026 @default.
• W2024957091 cites W2330980944 @default.
• W2024957091 cites W2332519193 @default.
• W2024957091 cites W2333755782 @default.
• W2024957091 cites W2334569155 @default.
• W2024957091 cites W2334629408 @default.
• W2024957091 cites W2335275228 @default.
• W2024957091 cites W2335281183 @default.
• W2024957091 cites W2335341899 @default.
• W2024957091 cites W2410612101 @default.
• W2024957091 cites W4247904703 @default.
• W2024957091 cites W53883515 @default.
• W2024957091 cites W560362396 @default.
• W2024957091 doi "https://doi.org/10.1038/sj.leu.2402925" @default.
• W2024957091 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12764369" @default.
• W2024957091 hasPublicationYear "2003" @default.
• W2024957091 type Work @default.
• W2024957091 sameAs 2024957091 @default.
• W2024957091 citedByCount "53" @default.
• W2024957091 countsByYear W20249570912013 @default.
• W2024957091 countsByYear W20249570912014 @default.
• W2024957091 countsByYear W20249570912015 @default.
• W2024957091 countsByYear W20249570912017 @default.
• W2024957091 countsByYear W20249570912020 @default.
• W2024957091 crossrefType "journal-article" @default.
• W2024957091 hasAuthorship W2024957091A5003308880 @default.
• W2024957091 hasAuthorship W2024957091A5003652463 @default.
• W2024957091 hasAuthorship W2024957091A5018679533 @default.
• W2024957091 hasAuthorship W2024957091A5030391285 @default.
• W2024957091 hasAuthorship W2024957091A5039157054 @default.
• W2024957091 hasAuthorship W2024957091A5047268135 @default.
• W2024957091 hasAuthorship W2024957091A5055448946 @default.
• W2024957091 hasAuthorship W2024957091A5059323796 @default.
• W2024957091 hasAuthorship W2024957091A5066385674 @default.
• W2024957091 hasAuthorship W2024957091A5073310914 @default.
• W2024957091 hasAuthorship W2024957091A5091807722 @default.
• W2024957091 hasBestOaLocation W20249570911 @default.
• W2024957091 hasConcept C104202773 @default.
• W2024957091 hasConcept C185592680 @default.

• next