Solution structure of ERK2 binding domain of MAPK phosphatase MKP-3: Structural insights into MKP-3 activation by ERK2

Amjad Farooq, Gaurav Chaturvedi, Shiraz Mujtaba, Olga Plotnikova, Lei Zeng, Christophe Dhalluin, Robert Ashton, Ming Ming Zhou

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MAP kinases (MAPKs), which control mitogenic signal transduction in all eukaryotic organisms, are inactivated by dual specificity MAPK phosphatases (MKPs). MKP-3, a prototypical MKP, achieves substrate specificity through its N-terminal domain binding to the MAPK ERK2, resulting in the activation of its C-terminal phosphatase domain. The solution structure and biochemical analysis of the ERK2 binding (EB) domain of MKP-3 show that regions that are essential for ERK2 binding partly overlap with its sites that interact with the C-terminal catalytic domain, and that these interactions are functionally coupled to the active site residues of MKP-3. Our findings suggest a novel mechanism by which the EB domain binding to ERK2 is transduced to cause a conformational change of the C-terminal catalytic domain, resulting in the enzymatic activation of MKP-3.

Original languageEnglish
Pages (from-to)387-399
Number of pages13
JournalMolecular Cell
Issue number2
StatePublished - Mar 22 2001
Externally publishedYes


ASJC Scopus subject areas

  • Molecular Biology

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