Research ArticleStructural Biology

A Distinct Interaction Mode Revealed by the Crystal Structure of the Kinase p38α with the MAPK Binding Domain of the Phosphatase MKP5

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Science Signaling  20 Dec 2011:
Vol. 4, Issue 204, pp. ra88
DOI: 10.1126/scisignal.2002241

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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.

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