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Cited by 1,156Protein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingSignaling Pathways in Disease

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MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo.

Sun, Hong, Charles, Catherine H., Lau, Lester F., Tonks, Nicholas K.·1993·Cell
DOI 10.1016/0092-8674(93)90383-2
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Abstract

Mitogenic stimulation of cells induces rapid and transient activation of MAP kinases. Here we report that a growth factor-inducible gene, 3CH134, encodes a dual specificity phosphatase that dephosphorylates and inactivates p42MAPK both in vitro and in vivo. In vitro, 3CH134 protein dephosphorylates both T183 and Y185 in p42MAPK. In serum-stimulated normal fibroblasts, the kinetics of inactivation of p42MAPK coincides with the appearance of newly synthesized 3CH134 protein, and the protein synthesis inhibitor cycloheximide leads to persistent activation of MAP kinase. Expression of 3CH134 in COS cells leads to selective dephosphorylation of p42MAPK from the spectrum of phosphotyrosyl proteins. 3CH134 blocks phosphorylation and activation of p42MAPK mediated by serum, oncogenic Ras, or activated Raf, whereas the catalytically inactive mutant of the phosphatase, Cys-258-->Ser, augments MAP kinase phosphorylation under similar conditions. The mutant 3CH134 protein also forms a physical complex with the phosphorylated form of p42MAPK. These findings suggest that 3CH134 is a physiological MAP kinase phosphatase; we propose the name MKP-1 for this phosphatase.

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References 32 · Cited by 1,156

Research works printed but not linked: 24

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Metadata

Authors
Sun, H., Charles, C. H., Lau, L. F., & Tonks, N. K.
Affiliations
  • Cold Spring Harbor Laboratory (US)
  • University of Illinois Chicago (US)
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
1993-11
Volume
75
Issue
3
Pages
487-493
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/0092-8674(93)90383-2
OpenAlex
W2115701574
Cited by
1,156
References
32
Citations by year
2026: 4 · 2025: 5 · 2024: 3 · 2023: 6 · 2022: 7 · 2021: 10 · 2020: 13 · 2019: 14 · 2018: 3 · 2017: 22 · 2016: 17 · 2015: 11 · 2014: 20 · 2013: 21 · 2012: 33
FWCI
31.67
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders
National Cancer Institute (CA52220, R01CA052220, CA53840)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
MKP-1, dual-specificity phosphatase, MAP kinase dephosphorylation, p42 MAP kinase, immediate early genes, growth factor signaling, oncogenic Ras, Raf, protein dephosphorylation, MAP kinase phosphatase
MeSH terms
Amino Acid Sequence, Animals, Cells, Cultured, Enzyme Activation, Molecular Sequence Data, Phosphoprotein Phosphatases, Substrate Specificity, Transfection, Retroviridae Proteins, Oncogenic, Oncogene Protein p21(ras), Gene Expression Regulation, Enzymologic, Protein Tyrosine Phosphatases, Calcium-Calmodulin-Dependent Protein Kinases, Immediate-Early Proteins, Cell Cycle Proteins, Oncogene Proteins v-raf, Macromolecular Substances, Dual Specificity Phosphatase 1, Protein Phosphatase 1

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