Akt phosphorylation site found in human caspase-9 is absent in mouse caspase-9

Biochem Biophys Res Commun. 1999 Oct 22;264(2):550-5. doi: 10.1006/bbrc.1999.1387.


Caspase-9 is one caspase upstream of caspase-3 and its activation is stimulated by Apaf-1/cytochrome c and inhibited by Akt signals. BAD phosphorylation by Akt is an essential step for growth factor-mediated inhibition of caspase activation. Recently, it was shown that human caspase-9 is phosphorylated by Akt and that its protease activity is reduced. To clarify the molecular mechanism of regulation of caspase-9 activation in neuronal apoptosis, we isolated two alternative splicing products of mouse caspase-9, caspase-9L and caspase-9S, from a P19 embryonal carcinoma cell cDNA library. Curiously, the Akt phosphorylation sites and motifs found in human caspase-9 were absent in both mouse caspase-9L and -9S. Mouse caspase-9 was not phosphorylated by activated Akt in vitro. Reverse transcription polymerase chain reaction analysis showed that the absent Akt motif is not limited to caspase-9 expressed in P19 embryonal carcinoma cells but also occurs in caspase-9 expressed in mouse, rat, and monkey. These results suggest that inhibition of caspase-9 activation by Akt-dependent phosphorylation is not generalized across species.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Caspases / chemistry
  • Caspases / genetics*
  • Caspases / metabolism
  • Cell Differentiation
  • Enzyme Activation
  • Gene Library
  • Humans
  • Mice
  • Molecular Sequence Data
  • Phosphorylation
  • Tumor Cells, Cultured


  • Caspases

Associated data

  • GENBANK/AB019600
  • GENBANK/AB019601