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

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

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
Volume7
Issue number2
DOIs
StatePublished - Mar 22 2001
Externally publishedYes

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Mitogen-Activated Protein Kinase Phosphatases
Phosphoric Monoester Hydrolases
Phosphotransferases
Catalytic Domain
Substrate Specificity
Signal Transduction

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Solution structure of ERK2 binding domain of MAPK phosphatase MKP-3 : Structural insights into MKP-3 activation by ERK2. / Farooq, Amjad; Chaturvedi, Gaurav; Mujtaba, Shiraz; Plotnikova, Olga; Zeng, Lei; Dhalluin, Christophe; Ashton, Robert; Zhou, Ming Ming.

In: Molecular Cell, Vol. 7, No. 2, 22.03.2001, p. 387-399.

Research output: Contribution to journalArticle

Farooq, A, Chaturvedi, G, Mujtaba, S, Plotnikova, O, Zeng, L, Dhalluin, C, Ashton, R & Zhou, MM 2001, 'Solution structure of ERK2 binding domain of MAPK phosphatase MKP-3: Structural insights into MKP-3 activation by ERK2', Molecular Cell, vol. 7, no. 2, pp. 387-399. https://doi.org/10.1016/S1097-2765(01)00186-1
Farooq, Amjad ; Chaturvedi, Gaurav ; Mujtaba, Shiraz ; Plotnikova, Olga ; Zeng, Lei ; Dhalluin, Christophe ; Ashton, Robert ; Zhou, Ming Ming. / Solution structure of ERK2 binding domain of MAPK phosphatase MKP-3 : Structural insights into MKP-3 activation by ERK2. In: Molecular Cell. 2001 ; Vol. 7, No. 2. pp. 387-399.
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