Study on the mechanism of the Notch-mediated Akt activation
Date Issued
2008
Date
2008
Author(s)
Yang, Yu-Hsuan
Abstract
Notch signaling regulate several key biological functions, Notch inhibits apoptosis through activation of PI3K-Akt signaling. The mechanism how Notch activates PI3K-Akt remains unclear. In this study, we examined three possible mechanisms involved in the activation of Akt by Notch. First, Notch may activate Akt through transcription activation of target genes. Second, Notch may activate Lck for subsequent activation of Akt. Third, Notch may stimulate Akt through enhanced XIAP signaling. We first used Notch ligands Jagged1 and Delta-like ligand1(DLL1) to stimulate DO11.10 T cell hybridoma and NIH3T3 fibroblast, and detected Akt phosphorylation, confirming the capacity of Notch to activate Akt. To determine the requirement of Notch transcription activity, we used different mutants carrying truncated forms of Notch intracellular domain (NICD). To study the potential involvement of Lck, Notch induced Akt activation was evaluated by using Lck inhibitor to block Lck activation. To investigate the possible involvement of XIAP, effect on Akt activation was determined when XIAP was either overexpressed or downregulated. We found similarity and difference between DO11.10 and NIH3T3 cells on the activation of Akt by Notch. In DO11.10 cells, the activation of Akt by Notch requires the transcription activity of Notch, Lck activation, and presence of XIAP. In NIH3T3 cells, the activation of Akt by Notch is involved the transcription activity of Notch and its transcription-inactive TAD domain, acting in unknown mechanism, but not XIAP. Our results illustrate the involvement of multiple signaling molecules in Notch-stimulated Akt activation, and point to the necessity for further investigation the detailed activation mechanisms.
Subjects
Notch
Akt activation
File(s)![Thumbnail Image]()
Loading...
Name
ntu-97-R95449011-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):796dca865d6ec3ccd9b7a98ea172da84