Caspase-3-mediated cleavage of Akt: involvement of non-consensus sites and influence of phosphorylation.
Here, we show for the first time that Akt1 is cleaved in vitro at the caspase-3 consensus site DQDD(456) downward arrow SM. Our data suggest QEEE(116) downward arrow E(117) downward arrow MD, EEMD(119) downward arrow, TPPD(453) downward arrow QD and DAKE(398) downward arrow IM as novel non-consensus caspase-3 cleavage sites. More importantly, we demonstrate that phosphorylation of Akt1 modulates its cleavage in a site-specific manner: Resistance to cleavage at site DAKE(398) (within the kinase domain) in response to phosphorylation suggests a possible mechanism by which the anti-apoptotic role of Akt1 is regulated. Our result is important in biological models which rely on Akt1 for cell survival.
Jahani-Asl
Arezu
A
Department of Obstetrics and Gynaecology, University of Ottawa, Ottawa, Canada.
Basak
Ajoy
A
Tsang
Benjamin K
BK
D020816:Amino Acid Motifs; D001665:Binding Sites; D053148:Caspase 3 / Q000502:physiology*; D016384:Consensus Sequence; D006801:Humans; D066298:In Vitro Techniques; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry* / Q000378:metabolism*; D020539:Sequence Analysis, Protein
D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; C505407:CASP3 protein, human; D053148:Caspase 3