Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 20 December 2011
Vol. 4, Issue 204, p. ra88
[DOI: 10.1126/scisignal.2002241]

RESEARCH ARTICLES

Editor's Summary

Docking the Kinase to the Phosphatase
The mitogen-activated protein kinase (MAPK) p38α promotes inflammation in diseases such as psoriasis, rheumatoid arthritis, and chronic obstructive pulmonary disease. Drugs that decrease the activity of p38α have been developed to treat these diseases; however, these compounds tend to have side effects that limit their clinical utility because they target a site in p38α that is conserved in other kinases. Phosphorylated or active p38α is dephosphorylated by the MAPK phosphatase 5 (MKP5). Zhang et al. (see also the Perspective by Goldsmith) report the crystal structure of the p38α-binding domain of MKP5 with p38α and show that these two proteins dock in a way that is distinct from that seen for other MAPKs and their phosphatases. Thus, the unconventional interaction between p38α and MKP5 could lead to the development of drugs that specifically act on p38α.

Citation: Y.-Y. Zhang, J.-W. Wu, Z.-X. Wang, A Distinct Interaction Mode Revealed by the Crystal Structure of the Kinase p38α with the MAPK Binding Domain of the Phosphatase MKP5. Sci. Signal. 4, ra88 (2011).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Structural Basis for the Regulation of the Mitogen-activated Protein (MAP) Kinase p38{alpha} by the Dual Specificity Phosphatase 16 MAP Kinase Binding Domain in Solution.
G. S. Kumar, H. Zettl, R. Page, and W. Peti (2013)
J. Biol. Chem. 288, 28347-28356
   Abstract »    Full Text »    PDF »
A Toxoplasma dense granule protein, GRA24, modulates the early immune response to infection by promoting a direct and sustained host p38 MAPK activation.
L. Braun, M.-P. Brenier-Pinchart, M. Yogavel, A. Curt-Varesano, R.-L. Curt-Bertini, T. Hussain, S. Kieffer-Jaquinod, Y. Coute, H. Pelloux, I. Tardieux, et al. (2013)
J. Exp. Med. 210, 2071-2086
   Abstract »    Full Text »    PDF »
A High-throughput Assay for Phosphoprotein-specific Phosphatase Activity in Cellular Extracts.
A. K. Bose and K. A. Janes (2013)
Mol. Cell. Proteomics 12, 797-806
   Abstract »    Full Text »    PDF »
New Therapeutic Targets in Cardiology: p38 Alpha Mitogen-Activated Protein Kinase for Ischemic Heart Disease.
E. D. Martin, G. F. De Nicola, and M. S. Marber (2012)
Circulation 126, 357-368
   Full Text »    PDF »
Three-Dimensional Docking in the MAPK p38{alpha}.
E. J. Goldsmith (2011)
Science Signaling 4, pe47
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882