Akt1-Mediated Phosphorylation of RBP-Jk Controls Notch1 Signaling

The Notch1 signaling pathway plays a crucial role in determining cell fate, including cell growth and differentiation. In this study, we demonstrated that the antagonistic action of RTK (receptor tyrosine kinase) signaling pathway on the Notch1 signaling pathway is mediated via Ras-PI3K-Akt1. The PI...

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Bibliographic Details
Published in:Biochemistry (Moscow) 2019-12, Vol.84 (12-13), p.1537-1546
Main Authors: Kim, M.-Y., Park, J. Y., Park, H.-S.
Format: Article
Language:English
Subjects:
AKT1 protein
Analysis
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Cellular signal transduction
Immunoglobulin J Recombination Signal Sequence-Binding Protein - metabolism
Influence
Kinases
Life Sciences
Methods
Mice
Microbiology
NIH 3T3 Cells
Notch1 protein
Observations
Oncogenes
Phosphorylation
Proto-Oncogene Proteins c-akt - metabolism
Receptor, Notch1 - metabolism
Recombinant proteins
Signal Transduction
Transcription, Genetic
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Summary:The Notch1 signaling pathway plays a crucial role in determining cell fate, including cell growth and differentiation. In this study, we demonstrated that the antagonistic action of RTK (receptor tyrosine kinase) signaling pathway on the Notch1 signaling pathway is mediated via Ras-PI3K-Akt1. The PI3K-Akt1 signaling pathway was shown to inhibit Notch1 signaling via phosphorylation of RBP-Jk. We observed not only reduced association between Notch1 and RBP-Jk, but also suppression of the Notch1 transcriptional activity. Our results demonstrated that Akt1 functions as a natural inhibitor of the Notch1 signaling pathway via phosphorylation of RBP-Jk.
ISSN:0006-2979
1608-3040
DOI:10.1134/S0006297919120137