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Sphingosine kinase‐1 is cleaved by cathepsin B in vitro: Identification of the initial cleavage sites for the protease
Author(s) -
Taha Tarek A.,
El-Alwani Mazen,
Hannun Yusuf A.,
Obeid Lina M.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.09.070
Subject(s) - cleavage (geology) , cathepsin o , cathepsin a , cysteine protease , cathepsin b , cathepsin , protease , biochemistry , chemistry , cleavage factor , cathepsin h , sphingosine , microbiology and biotechnology , cathepsin e , enzyme , biology , paleontology , receptor , fracture (geology) , messenger rna , gene
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.