Matches in SemOpenAlex for { <https://semopenalex.org/work/W2059884146> ?p ?o ?g. }
- W2059884146 endingPage "1642" @default.
- W2059884146 startingPage "1630" @default.
- W2059884146 abstract "The 90 kDa ribosomal S6 kinases (RSK) are effectors of the Ras-ERK1/2 signaling pathway. RSK signaling controls proliferation and protein synthesis, and is altered in several types of tumors. BI-D1870 and SL0101 are two widely used inhibitors of RSK. After revision of the literature, discrepancies in the effects of the inhibitors were identified. Herein we report that while SL0101 inhibited mTORC1-p70S6K signaling, BI-D1870 increased p70S6K activation. Both effects were independent of ERK1/2 and RSK, and thus nonspecific. We also demonstrated how these opposite nonspecific effects mislead the identification of the RSK-dependent phosphorylation of rpS6 (S235/236), a known RSK and p70S6K substrate. Phosphorylation of tuberin at S1798 by RSK was proposed to mediate ERK1/2-dependent activation of mTORC1-p70S6K signaling. In glioblastoma-derived cells, phosphorylation of tuberin was abolished after RSK depletion or ERK1/2 inhibition, suggesting that RSK is its main kinase. However, RSK depletion did not reduce PMA-dependent p70S6K phosphorylation, which suggests that tuberin phosphorylation at S1798 is not the main mediator of ERK1/2-dependent activation of mTORC1. Remarkably, tuberin phosphorylation (S1798) followed the activation status of RSK in different cells and experimental conditions, suggesting that phosphorylation of that residue could be used as readout for RSK activation in cells. We confirmed the difference in the effects of SL0101 and BI-D1870 in cellular proliferation assays. Rapamycin potentiated the inhibition of proliferation induced by BI-D1870, but not by SL0101. We thus conclude that SL0101 and BI-D1870 induce distinct off-target effects in mTORC1-p70S6K signaling, and thus, the functions previously ascribed to RSK based on these inhibitors should be reassessed." @default.
- W2059884146 created "2016-06-24" @default.
- W2059884146 creator A5003822369 @default.
- W2059884146 creator A5023933328 @default.
- W2059884146 creator A5036875637 @default.
- W2059884146 creator A5076740367 @default.
- W2059884146 creator A5089215195 @default.
- W2059884146 date "2015-08-01" @default.
- W2059884146 modified "2023-10-01" @default.
- W2059884146 title "Two widely used RSK inhibitors, BI-D1870 and SL0101, alter mTORC1 signaling in a RSK-independent manner" @default.
- W2059884146 cites W1968180930 @default.
- W2059884146 cites W1970600179 @default.
- W2059884146 cites W1975673963 @default.
- W2059884146 cites W1987438955 @default.
- W2059884146 cites W1990797315 @default.
- W2059884146 cites W1990853098 @default.
- W2059884146 cites W1993169124 @default.
- W2059884146 cites W1995496043 @default.
- W2059884146 cites W1997746865 @default.
- W2059884146 cites W1998203489 @default.
- W2059884146 cites W1998682097 @default.
- W2059884146 cites W2006404179 @default.
- W2059884146 cites W2008102952 @default.
- W2059884146 cites W2011113518 @default.
- W2059884146 cites W2011913495 @default.
- W2059884146 cites W2015714994 @default.
- W2059884146 cites W2017622605 @default.
- W2059884146 cites W2023747548 @default.
- W2059884146 cites W2028704745 @default.
- W2059884146 cites W2031995640 @default.
- W2059884146 cites W2033182904 @default.
- W2059884146 cites W2036753586 @default.
- W2059884146 cites W2036900657 @default.
- W2059884146 cites W2042625441 @default.
- W2059884146 cites W2046822015 @default.
- W2059884146 cites W2052615604 @default.
- W2059884146 cites W2055830948 @default.
- W2059884146 cites W2058138221 @default.
- W2059884146 cites W2061489261 @default.
- W2059884146 cites W2063845207 @default.
- W2059884146 cites W2064854415 @default.
- W2059884146 cites W2074883812 @default.
- W2059884146 cites W2083990797 @default.
- W2059884146 cites W2086675688 @default.
- W2059884146 cites W2089855272 @default.
- W2059884146 cites W2100170827 @default.
- W2059884146 cites W2105029267 @default.
- W2059884146 cites W2107495112 @default.
- W2059884146 cites W2110054974 @default.
- W2059884146 cites W2114869204 @default.
- W2059884146 cites W2121727754 @default.
- W2059884146 cites W2125666085 @default.
- W2059884146 cites W2132349803 @default.
- W2059884146 cites W2134757689 @default.
- W2059884146 cites W2138961421 @default.
- W2059884146 cites W2139440218 @default.
- W2059884146 cites W2143227312 @default.
- W2059884146 cites W2148561037 @default.
- W2059884146 cites W2151856174 @default.
- W2059884146 cites W2151931061 @default.
- W2059884146 cites W2152086488 @default.
- W2059884146 cites W2154053380 @default.
- W2059884146 cites W2158326728 @default.
- W2059884146 cites W2160219683 @default.
- W2059884146 cites W2160226692 @default.
- W2059884146 cites W2162474938 @default.
- W2059884146 cites W2164462432 @default.
- W2059884146 cites W2165558270 @default.
- W2059884146 cites W2166307667 @default.
- W2059884146 cites W4238567307 @default.
- W2059884146 cites W65155625 @default.
- W2059884146 doi "https://doi.org/10.1016/j.cellsig.2015.04.004" @default.
- W2059884146 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25889895" @default.
- W2059884146 hasPublicationYear "2015" @default.
- W2059884146 type Work @default.
- W2059884146 sameAs 2059884146 @default.
- W2059884146 citedByCount "32" @default.
- W2059884146 countsByYear W20598841462015 @default.
- W2059884146 countsByYear W20598841462016 @default.
- W2059884146 countsByYear W20598841462017 @default.
- W2059884146 countsByYear W20598841462018 @default.
- W2059884146 countsByYear W20598841462019 @default.
- W2059884146 countsByYear W20598841462020 @default.
- W2059884146 countsByYear W20598841462021 @default.
- W2059884146 countsByYear W20598841462022 @default.
- W2059884146 countsByYear W20598841462023 @default.
- W2059884146 crossrefType "journal-article" @default.
- W2059884146 hasAuthorship W2059884146A5003822369 @default.
- W2059884146 hasAuthorship W2059884146A5023933328 @default.
- W2059884146 hasAuthorship W2059884146A5036875637 @default.
- W2059884146 hasAuthorship W2059884146A5076740367 @default.
- W2059884146 hasAuthorship W2059884146A5089215195 @default.
- W2059884146 hasConcept C104202773 @default.
- W2059884146 hasConcept C11960822 @default.
- W2059884146 hasConcept C184235292 @default.
- W2059884146 hasConcept C2780044377 @default.
- W2059884146 hasConcept C2780926556 @default.
- W2059884146 hasConcept C51785407 @default.