We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Delineation of exoenzyme S residues that mediate the interaction with 14-3-3 and its biological activity.
- Authors
Yasmin, Lubna; Jansson, Anna L.; Panahandeh, Tooba; Palmer, Ruth H.; Francis, Matthew S.; Hallberg, Bengt
- Abstract
14-3-3 proteins belong to a family of conserved molecules expressed in all eukaryotic cells, which play an important role in a multitude of signaling pathways. 14-3-3 proteins bind to phosphoserine/phosphothreonine motifs in a sequence-specific manner. More than 200 14-3-3 binding partners have been found that are involved in cell cycle regulation, apoptosis, stress responses, cell metabolism and malignant transformation. A phosphorylation-independent interaction has been reported to occur between 14-3-3 and a C-terminal domain within exoenzyme S (ExoS), a bacterial ADP-ribosyltransferase toxin from Pseudomonas aeruginosa. In this study, we have investigated the effect of amino acid mutations in this C-terminal domain of ExoS on ADP-ribosyltransferase activity and the 14-3-3 interaction. Our results suggest that leucine-428 of ExoS is the most critical residue for ExoS enzymatic activity, as cytotoxicity analysis reveals that substitution of this leucine significantly weakens the ability of ExoS to mediate cell death. Leucine-428 is also required for the ability of ExoS to modify the eukaryotic endogenous target Ras. Finally, single amino acid substitutions of positions 426–428 reduce the interaction potential of 14-3-3 with ExoS in vitro.
- Subjects
ADP-ribosylation; CELLULAR signal transduction; COENZYMES; CELL-mediated cytotoxicity; CYSTIC fibrosis; PSEUDOMONAS aeruginosa
- Publication
FEBS Journal, 2006, Vol 273, Issue 3, p638
- ISSN
1742-464X
- Publication type
Article
- DOI
10.1111/j.1742-4658.2005.05100.x