Translation inhibitors in chronically activated PDGFRA cells (Homo sapiens)

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1, 2ChronicTranslation initiationDegradationCAP dependent translationPDK1PRKCDRPS6KA4AKT1RPS6KA1RPS6KB1RPS6KB24EGI-1MTORMAPK14PIM15' TOP mRNA translationAZD8055RPS6PDCD4MAP2K4PRPTORPPMAP2K1PPMAPK1PPMAPK3PPMAP2K2PPPIK3CAPIK3CBPIK3R1PIK3R2PIK3R3PIK3CGMAP2K5MAP2K6MAP2K7MAPK9MAPK10MAPK8MAP2K3MAP2K6PRKCARPS6KA5CSNK2A1PRKACARPS6KA2AKT2AKT3RPS6EIF4EBP1EIF4EEIF4EBP1PPPPDCD4PPEIF4A1EIF4A2EIF4G3EIF4G1EIF4A1EIF4A2EIF4EPIM2EIF4BPEIF4BEIF4G3EIF4G1EIF4A1EIF4A2EIF4EEIF4BPLY2584702ChronicAcuteAcute


Description

Chronic stimulation of the PDGFRA receptor results in decreased phosphorylation of RSK1/2 and S6K1/2, which subsequently impairs the phosphorylation of S6 ribosome protein and associated ribosome biogenesis and 5′ TOP mRNA translation. The phosphorylation of 4EBP1 and PDCD4 are suppressed, which subsequently limits the components of the eIF4F complex (eIF4E and eIF4A) from joining into the complex. In addition, the phosphorylation of the translation initiation factor eIF4B is also decreased. These changes result in a suppressed CAP-dependent translation initiation in cells with chronic stimulated PDGFRA signaling compared with acute stimulated ones. Based on figure S7 from Zhou et al. Protein phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.

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Bibliography

  1. Zhou S, Appleman VA, Rose CM, Jun HJ, Yang J, Zhou Y, Bronson RT, Gygi SP, Charest A; ''Chronic platelet-derived growth factor receptor signaling exerts control over initiation of protein translation in glioma.''; Life Sci Alliance, 2018 PubMed Europe PMC Scholia
  2. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E; ''PhosphoSitePlus, 2014: mutations, PTMs and recalibrations.''; Nucleic Acids Res, 2015 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
134745view23:23, 26 July 2024EweitzRestore state marker positions
134744view23:20, 26 July 2024EweitzStandardize case
134743view23:19, 26 July 2024EweitzEconomize layout
127382view19:45, 26 September 2023Khanspersupdated phospho sites
127254view17:45, 28 August 2023KhanspersAdded literature ref and updated description
104315view19:58, 16 May 2019Khanspersconnected interaction
103809view05:31, 9 April 2019AlexanderPicoModified title
103808view05:27, 9 April 2019AlexanderPicoModified title
103807view05:27, 9 April 2019AlexanderPicoModified description
103749view22:21, 3 April 2019Khansperslabels
103748view22:15, 3 April 2019KhanspersModified description
103747view22:15, 3 April 2019KhanspersModified description
103746view22:10, 3 April 2019Khanspersupdated phosphosites
103738view20:29, 2 April 2019DeSlChanged secondary to primary ChEBI ID for AZD8055.
103727view19:55, 31 March 2019Andraadded metabolite identifier
103725view23:05, 29 March 2019KhanspersOntology Term : 'glioma pathway' added !
103724view23:04, 29 March 2019KhanspersOntology Term : 'translation initiation pathway' added !
103723view23:02, 29 March 2019KhanspersModified title
103722view23:01, 29 March 2019KhanspersNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
4EGI-1Metabolite6911989 (PubChem-compound)
5' TOP mRNA translationPathway
AKT1GeneProductENSG00000142208 (Ensembl)
AKT2GeneProductENSG00000105221 (Ensembl)
AKT3GeneProductENSG00000117020 (Ensembl)
AZD8055MetaboliteCHEBI:91329 (ChEBI)
CSNK2A1GeneProductENSG00000101266 (Ensembl)
EIF4A1GeneProduct1973 (Entrez Gene)
EIF4A2GeneProduct1974 (Entrez Gene)
EIF4BGeneProduct1975 (Entrez Gene)
EIF4EGeneProduct1977 (Entrez Gene)
EIF4EBP1GeneProduct1978 (Entrez Gene)
EIF4G1GeneProduct1981 (Entrez Gene) TrEMBL accession number O43177 refers to same protein.
EIF4G3GeneProduct8672 (Entrez Gene)
LY2584702Metabolite
MAP2K1GeneProduct5604 (Entrez Gene)
MAP2K2GeneProduct5605 (Entrez Gene)
MAP2K3GeneProductENSG00000034152 (Ensembl)
MAP2K4GeneProductENSG00000065559 (Ensembl)
MAP2K5GeneProductENSG00000137764 (Ensembl)
MAP2K6GeneProductENSG00000108984 (Ensembl)
MAP2K7GeneProductENSG00000076984 (Ensembl)
MAPK10GeneProduct5602 (Entrez Gene)
MAPK14GeneProductENSG00000112062 (Ensembl)
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
MAPK8GeneProduct5599 (Entrez Gene)
MAPK9GeneProduct5601 (Entrez Gene)
MTORGeneProductENSG00000198793 (Ensembl)
PDCD4GeneProductENSG00000150593 (Ensembl)
PDK1GeneProductENSG00000152256 (Ensembl)
PIK3CAGeneProductENSG00000121879 (Ensembl)
PIK3CBGeneProductENSG00000051382 (Ensembl)
PIK3CGGeneProductENSG00000105851 (Ensembl)
PIK3R1GeneProductENSG00000145675 (Ensembl)
PIK3R2GeneProductENSG00000105647 (Ensembl)
PIK3R3GeneProductENSG00000117461 (Ensembl)
PIM1GeneProductENSG00000137193 (Ensembl)
PIM2GeneProductENSG00000102096 (Ensembl)
PRKACAGeneProductENSG00000072062 (Ensembl)
PRKCAGeneProductENSG00000154229 (Ensembl)
PRKCDGeneProductENSG00000163932 (Ensembl)
RPS6GeneProductENSG00000137154 (Ensembl)
RPS6KA1GeneProductENSG00000117676 (Ensembl)
RPS6KA2GeneProductENSG00000071242 (Ensembl)
RPS6KA4GeneProductENSG00000162302 (Ensembl)
RPS6KA5GeneProductENSG00000100784 (Ensembl)
RPS6KB1GeneProductENSG00000108443 (Ensembl)
RPS6KB2GeneProductENSG00000175634 (Ensembl)
RPTORGeneProductENSG00000141564 (Ensembl)

Annotated Interactions

No annotated interactions

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