title: Akt phosphorylation site found in human caspase-9 is absent in mouse caspase-9.
abstract: 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.
authors.affiliation: Division of Development and Differentiation, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Fujita
authors.forename: A
authors.initials: A
authors.lastname: Jinbo
authors.forename: H
authors.initials: H
authors.lastname: Matuzaki
authors.forename: H
authors.initials: H
authors.lastname: Konishi
authors.forename: U
authors.initials: U
authors.lastname: Kikkawa
authors.forename: T
authors.initials: T
authors.lastname: Momoi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020169:Caspases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D004789:Enzyme Activation; D015723:Gene Library; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D014407:Tumor Cells, Cultured
chemical_list: D020169:Caspases