What question did this study set out to answer?

To elucidate the mechanism of substrate-mediated catalytic activation and binding specificity of MAP kinase phosphatase-3 (MKP-3) by ERK2.

May 22, 1998Science

Catalytic Activation of the Phosphatase MKP-3 by ERK2 Mitogen-Activated Protein Kinase

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Authors

MCMontserrat CampsUniversitat Autònoma de Barcelona ANAnthony C. NicholsWestern University CGCorine GilliéronUniversity of Geneva

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Implication

Biochemical analysis reveals direct ERK2 binding catalytically activates MKP-3 phosphatase, indicating substrate binding directly regulates MAP kinase pathways.

Key Points

To elucidate the mechanism of substrate-mediated catalytic activation and binding specificity of MAP kinase phosphatase-3 (MKP-3) by ERK2.
Assayed in vitro binding and catalytic activation of purified MKP-3 using purified wild-type ERK2 and the Sevenmaker D319N ERK2 mutant.
Evaluated MKP-3 activation in the presence and absence of kinase activity using the noncatalytic amino-terminus domain of MKP-3.
Tested cross-reactivity and binding specificity with JNK/SAPK, p38 MAP kinases, and the homologous phosphatase MKP-4.
Direct binding of ERK2 to the noncatalytic amino-terminus of MKP-3 induced catalytic activation independent of ERK2 protein kinase activity.
The ERK2 D319N mutant, JNK/SAPK, and p38 MAP kinases failed to bind or catalytically activate MKP-3 and remained resistant to MKP-3-mediated dephosphorylation.
Homologous phosphatase MKP-4 displayed nonselective activation, binding and gaining catalytic activity in response to ERK2, JNK/SAPK, and p38 MAP kinases.

Cite This Study

Camps et al. (1998) studied this question.

synapsesocial.com/papers/6a7070fa6c240de38cdbcde1 https://doi.org/10.1126/science.280.5367.1262

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Implication

Biochemical analysis reveals direct ERK2 binding catalytically activates MKP-3 phosphatase, indicating substrate binding directly regulates MAP kinase pathways.

Catalytic Activation of the Phosphatase MKP-3 by ERK2 Mitogen-Activated Protein Kinase

Discussion

Member takes

Implication

Key Points

Cite This Study

Catalytic Activation of the Phosphatase MKP-3 by ERK2 Mitogen-Activated Protein Kinase

Discussion

Member takes

Implication

Key Points

Cite This Study

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