Sphingosine kinase‐1 is cleaved by cathepsin B in vitro: Identification of the initial cleavage sites for the protease
Open Access
- 12 October 2006
- journal article
- research article
- Published by Wiley in FEBS Letters
- Vol. 580 (26) , 6047-6054
- https://doi.org/10.1016/j.febslet.2006.09.070
Abstract
Previous work has identified sphingosine kinase‐1 (SK1) as a substrate for the cysteine protease cathepsin B in vitro. In this study, the mechanism of SK1 cleavage by cathepsin B was investigated. We identified two initial cleavage sites for the protease, the first at histidine 122 and the second at arginine 199. Mutation analysis showed that replacement of histidine 122 with a tyrosine maintained the activity of SK1 while significantly reducing cleavage by cathepsin B at the initial cleavage site. The efficacy of cleavage of SK1 at arginine 199, however, was not affected. These studies demonstrate that SK1 is cleaved by cathepsin B in a sequential manner after basic amino acids, and that the initial cleavages at the two identified sites occur independently of each other.Keywords
This publication has 26 references indexed in Scilit:
- Asp177 in C4 domain of mouse sphingosine kinase 1a is important for the sphingosine recognitionFEBS Letters, 2004
- Exon Skipping of Cathepsin BJournal of Biological Chemistry, 2004
- Selective Disruption of Lysosomes in HeLa Cells Triggers Apoptosis Mediated by Cleavage of Bid by Multiple Papain-like Lysosomal CathepsinsJournal of Biological Chemistry, 2004
- The Nucleotide-binding Site of Human Sphingosine Kinase 1Published by Elsevier ,2002
- PKC-dependent Activation of Sphingosine Kinase 1 and Translocation to the Plasma MembraneJournal of Biological Chemistry, 2002
- Interaction of Human Breast Fibroblasts with Collagen I Increases Secretion of Procathepsin BPublished by Elsevier ,2002
- Phorbol Ester Activation of a Proteolytic Cascade Capable of Activating Latent Transforming Growth Factor-βJournal of Biological Chemistry, 2002
- Lysosomal Protease Pathways to ApoptosisJournal of Biological Chemistry, 2001
- In VivoExpression of an Alternatively Spliced Human Tumor Message That Encodes a Truncated Form of Cathepsin BJournal of Biological Chemistry, 1998
- The selective role of cathepsins B and D in the lysosomal degradation of endogenous and exogenous proteinsFEBS Letters, 1991