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Title: Doxorubicin-induced activation of protein kinase D1 through caspase-mediated proteolytic cleavage: identification of two cleavage sites by microsequencing
Authors: Vántus, Tibor ×
Vertommen, Didier
Saelens, Xavier
Rykx, An
De Kimpe, Line
Vancauwenbergh, Sadia
Mikhalap, Svitlana
Waelkens, Etienne
Kéri, György
Seufferlein, Thomas
Vandenabeele, Peter
Rider, Mark H
Vandenheede, Jackie
Van Lint, Johan #
Issue Date: Jun-2004
Publisher: Pergamon Press
Series Title: Cellular Signalling vol:16 issue:6 pages:703-709
Abstract: Recent studies have demonstrated the importance of protein kinase D (PKD) in cell proliferation and apoptosis. Here, we report that in vitro cleavage of recombinant PKD1 by caspase-3 generates two alternative active PKD fragments. N-terminal sequencing of these fragments revealed two distinct caspase-3 cleavage sites located between the acidic and pleckstrin homology (PH) domains of PKD1. Moreover, we present experimental evidence that PKD1 is an in vitro substrate for both initiator and effector caspases. During doxorubicin-induced apoptosis, a zVAD-sensitive caspase induces cleavage of PKD1 at two sites, generating fragments with the same molecular masses as those determined in vitro. The in vivo caspase-dependent generation of the PKD1 fragments correlates with PKD1 kinase activation. Our results indicate that doxorubicin-mediated apoptosis induces activation of PKD1 through a novel mechanism involving the caspase-mediated proteolysis.
ISSN: 0898-6568
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Biochemistry Section (Medicine) (-)
Department of Cellular and Molecular Medicine - miscellaneous
Laboratory of Biosignaling & Therapeutics
Laboratory of Protein Phosphorylation and Proteomics
Laboratory of Phosphoproteomics (-)
× corresponding author
# (joint) last author

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