Identification of proteolytic fragments from ErbB-2 that induce apoptosis.
The receptor tyrosine kinase ErbB-2 plays an important role in cell proliferation and differentiation as well as oncogenesis. We have found that ErbB-2 kinase domain fragmentation is important for the induction of apoptosis. Exogenous expression of peptides derived from the ErbB-2 kinase domain induces cells death with the hallmarks of apoptosis. In contrast, transfection of the ErbB-2 carboxy-terminal domain did not induce apoptosis. We have identified a 37-residue segment from the ErbB-2 kinase N-terminal lobe that can strongly induce apoptosis in transfected cells. Cell death was not blocked by the pan-caspase inhibitor z-VAD-FMK. Similar fragments derived from several other receptor tyrosine kinases also induce cell death. These data imply that proteolytic fragmentation of tyrosine kinases liberates apoptotic fragments that can accelerate cell death.
Tikhomirov
Oleg
O
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
Dikov
Mikhail
M
Carpenter
Graham
G
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*
D049452:Green Fluorescent Proteins; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases