VopA Inhibits ATP Binding by Acetylating the Catalytic Loop of MAPK Kinases
| Autor: | Kim Orth, Jennifer E. Trosky, Sohini Mukherjee, Yan Li, Gladys J. Keitany, Haydn L. Ball |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
MAP Kinase Signaling System
Bacterial Toxins Lysine Amino-Acid N-Acetyltransferase Biology Biochemistry MKKS Cell Line Mice Adenosine Triphosphate Animals Kinase activity Molecular Biology Mitogen-Activated Protein Kinase Kinases Kinase fungi Acetylation Cell Biology Cell biology Adenosine Diphosphate Enzyme Activation Vibrio Infections Acetyltransferase Phosphorylation Vibrio parahaemolyticus Signal transduction Protein Processing Post-Translational Bacterial Outer Membrane Proteins |
| Zdroj: | Journal of Biological Chemistry. 282:34299-34305 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m706970200 |
| Popis: | The bacterial pathogen Vibrio parahemeolyticus manipulates host signaling pathways during infections by injecting type III effectors. One of these effectors, Vibrio outer protein A (VopA), inhibits MAPK signaling via a novel mechanism, distinct from those described for other bacterial toxins, that disrupts this signaling pathway. VopA is an acetyltransferase that potently inhibits MAPK signaling pathways not only by preventing the activation of MAPK kinases (MKKs) but also by inhibiting the activity of activated MKKs. VopA acetylates a conserved lysine found in the catalytic loop of all kinases and blocks the binding of ATP, but not ADP, on the MKKs, resulting in an inactive phosphorylated kinase. Acetylation of this conserved lysine inhibits kinase activity by a new mechanism of regulation that has not been observed previously. Identifying the target of VopA reveals a way that the reversible post-translational modification of lysine acetylation can be used to regulate the activity of an enzyme. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|