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Logo of jbcThe Journal of Biological Chemistry
J Biol Chem. 2013 September 27; 288(39): 28357.
PMCID: PMC3784752

Mapping the Interaction between the Mitogen-activated Protein Kinase p38α and Its Regulatory Phosphatase♦

Structural Basis for the Regulation of the Mitogen-activated Protein (MAP) Kinase p38α by the Dual Specificity Phosphatase 16 MAP Kinase Binding Domain in Solution

♦ See referenced article, J. Biol. Chem. 2013, 288, 28347–28356

Mitogen-activated protein kinases (MAPKs) are critical in signal transduction pathways and are important pharmaceutical targets. Their activities are regulated by a number of proteins, including dual specificity phosphatases. In a Paper of the Week, a team lead by Wolfgang Peti at Brown University in Rhode Island demonstrated that one of these phosphatases, DUSP16, interacts with MAPK p38α in a way different from other dual specificity phosphatases. By looking at the solution structure of the two proteins using nuclear magnetic resonance and small-angle x-ray scattering as well as monitoring the binding by isothermal titration calorimetry, the investigators showed that the MAPK binding domain (MKBD) of DUSP16 uses an additional α-helix to interact with p38α and increases its binding strength. The authors say, “Together, these structural and energetic differences in p38α engagement highlight the fine-tuning necessary to achieve MAPK specificity and regulation among multiple regulatory proteins.”

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The DUSP16 MKBD interacts with p38α via helices α2, α3, and α4. Shown is a graphic surface structure of the DUSP16 MKBD.

Articles from The Journal of Biological Chemistry are provided here courtesy of American Society for Biochemistry and Molecular Biology