Translation inhibitors in chronically activated PDGFRA cells (WP4566)

Homo sapiens

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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 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238596/ Zhou et al]. Protein phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.

Authors

Kristina Hanspers , Andra Waagmeester , Denise Slenter , Alex Pico , and Eric Weitz

Activity

last edited

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Cited In

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Organisms

Homo sapiens

Communities

CPTAC ExRNA

Annotations

Pathway Ontology

glioma pathway translation initiation pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
AZD8055 Metabolite chebi:91329
4EGI-1 Metabolite pubchem.compound:6911989
PRKCD GeneProduct ensembl:ENSG00000163932
MAPK14 GeneProduct ensembl:ENSG00000112062
MAP2K4 GeneProduct ensembl:ENSG00000065559
RPS6KA1 GeneProduct ensembl:ENSG00000117676
RPS6 GeneProduct ensembl:ENSG00000137154
RPS6KA4 GeneProduct ensembl:ENSG00000162302
RPS6KB1 GeneProduct ensembl:ENSG00000108443
PIM1 GeneProduct ensembl:ENSG00000137193
PDK1 GeneProduct ensembl:ENSG00000152256
RPS6KB2 GeneProduct ensembl:ENSG00000175634
AKT1 GeneProduct ensembl:ENSG00000142208
PDCD4 GeneProduct ensembl:ENSG00000150593
MTOR GeneProduct ensembl:ENSG00000198793
RPTOR GeneProduct ensembl:ENSG00000141564
MAP2K1 GeneProduct ncbigene:5604
MAPK1 GeneProduct ncbigene:5594
MAPK3 GeneProduct ncbigene:5595
MAP2K2 GeneProduct ncbigene:5605
PIK3CA GeneProduct ensembl:ENSG00000121879
PIK3CB GeneProduct ensembl:ENSG00000051382
PIK3R1 GeneProduct ensembl:ENSG00000145675
PIK3R2 GeneProduct ensembl:ENSG00000105647
PIK3R3 GeneProduct ensembl:ENSG00000117461
PIK3CG GeneProduct ensembl:ENSG00000105851
MAP2K5 GeneProduct ensembl:ENSG00000137764
MAP2K6 GeneProduct ensembl:ENSG00000108984
MAP2K7 GeneProduct ensembl:ENSG00000076984
MAPK9 GeneProduct ncbigene:5601
MAPK10 GeneProduct ncbigene:5602
MAPK8 GeneProduct ncbigene:5599
MAP2K3 GeneProduct ensembl:ENSG00000034152
PRKCA GeneProduct ensembl:ENSG00000154229
RPS6KA5 GeneProduct ensembl:ENSG00000100784
CSNK2A1 GeneProduct ensembl:ENSG00000101266
PRKACA GeneProduct ensembl:ENSG00000072062
RPS6KA2 GeneProduct ensembl:ENSG00000071242
AKT2 GeneProduct ensembl:ENSG00000105221
AKT3 GeneProduct ensembl:ENSG00000117020
EIF4EBP1 GeneProduct ncbigene:1978
EIF4E GeneProduct ncbigene:1977
EIF4A1 GeneProduct ncbigene:1973
EIF4A2 GeneProduct ncbigene:1974
EIF4G3 GeneProduct ncbigene:8672
EIF4G1 GeneProduct ncbigene:1981 TrEMBL accession number O43177 refers to same protein.
PIM2 GeneProduct ensembl:ENSG00000102096
EIF4B GeneProduct ncbigene:1975

References

  1. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E. Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20. PubMed Europe PMC Scholia
  2. Chronic platelet-derived growth factor receptor signaling exerts control over initiation of protein translation in glioma. Zhou S, Appleman VA, Rose CM, Jun HJ, Yang J, Zhou Y, et al. Life Sci Alliance. 2018 Jun 19;1(3):e201800029. PubMed Europe PMC Scholia