Akt suppresses DLK for maintaining self-renewal of mouse embryonic stem cells

  • Cheng Chung Wu (貢獻者)
  • Chia Hui Lin (貢獻者)
  • Shu Ching Hsu (貢獻者)
  • Michael Hsiao (貢獻者)
  • Yi Rong Chen (貢獻者)
  • Nian-Han Ma (貢獻者)
  • Scott C. Schuyler (貢獻者)
  • Frank Leigh Lu (貢獻者)
  • Jean Lu (貢獻者)
  • Hong Jin Wu (貢獻者)
  • Chia Hui Wang (貢獻者)



Mouse embryonic stem cells (ES cells) can proliferate indefinitely. To identify potential signals involved in suppression of self-renewal, we previously screened a kinase/phosphatase expression library in ES cells, and observed that inhibition of Dual Leucine zipper-bearing Kinase (DLK) increased relative cell numbers. DLK protein was detected in both the pluripotent and differentiated states of mouse ES cells while DLK kinase activity increased upon differentiation. Overexpression of DLK in mouse ES cells displayed reductions in relative cell/colony numbers and Nanog expression, suggesting a suppressive role of DLK in self-renewal. By examining protein sequences of DLK, we identified 2 putative Akt phosphorylation sites at S584 and T659. Blocking PI3K/Akt signaling with LY-294002 enhanced DLK kinase activity dramatically. We found that Akt interacts with and phosphorylates DLK. Mutations of DLK amino acid residues at putative Akt phosphorylation sites (S584A, T659A, or S584A and T659A) diminished the level of DLK phosphorylation. While the mutated DLKs (S584A, T659A, or S584A and T659A) were expressed, a further reduction in cell/colony numbers and Nanog expression appeared in mouse ES cells. In addition, these mutant DLKs (S584A, T659A, or S584A and T659A) exhibited more robust kinase activity and cell death compared to wild type DLK or green fluorescence (GFP) controls. In summary, our results show that DLK functions to suppress self-renewal of mouse ES cells and is restrained by Akt phosphorylation.
可用日期1 1月 2015
發行者figshare Academic Research System
  • Akt suppresses DLK for maintaining self-renewal of mouse embryonic stem cells

    Wu, C. C., Wu, H. J., Wang, C. H., Lin, C. H., Hsu, S. C., Chen, Y. R., Hsiao, M., Schuyler, S. C., Leigh Lu, F., Ma, N. & Lu, J., 15 4月 2015, 於: Cell Cycle. 14, 8, p. 1207-1217 11 p.

    研究成果: 雜誌貢獻期刊論文同行評審

    13 引文 斯高帕斯(Scopus)