Cited by 1,555Protein Kinase Regulation and GTPase SignalingMelanoma and MAPK PathwaysProtein Tyrosine Phosphatases

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Independent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms

Dérijard, Benoit, Raingeaud, Joël, Barrett, Tamera, Wu, I-Huan, Han, Jiahuai, Ulevitch, Richard J., Davis, Roger J.·1995·Science

DOI 10.1126/science.7839144

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Abstract

Mammalian mitogen-activated protein (MAP) kinases include extracellular signal-regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38 subgroups. These MAP kinase isoforms are activated by dual phosphorylation on threonine and tyrosine. Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. These MKK isoforms did not activate the ERK subgroup of MAP kinases, but MKK4 did activate JNK. These data demonstrate that the activators of p38 (MKK3 and MKK4), JNK (MKK4), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways.

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Authors: Dérijard, B., Raingeaud, J., Barrett, T., Wu, I.-H., Han, J., Ulevitch, R. J., & Davis, R. J.
Affiliations: University of Massachusetts Chan Medical School (US)
ORCID: Han, Jiahuai
Ulevitch, Richard J.
Davis, Roger J.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1995-02-03
Volume: 267
Issue: 5198
Pages: 682-685
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.7839144
OpenAlex: W1998487776
Cited by: 1,555
References: 29
Citations by year: 2026: 8 · 2025: 9 · 2024: 9 · 2023: 12 · 2022: 16 · 2021: 19 · 2020: 14 · 2019: 20 · 2018: 16 · 2017: 19 · 2016: 24 · 2015: 15 · 2014: 27 · 2013: 25 · 2012: 27
FWCI: 53.10
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ca058396-09)
National Cancer Institute (CA 58396)
National Institute of General Medical Sciences (GM 37696, P01GM037696)
National Institute of Allergy and Infectious Diseases (AI 15136, R01AI015136)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords: MAPK signaling, MKK3, MKK4, p38 MAPK, ERK, JNK, signaling pathways, dual phosphorylation
MeSH terms: Amino Acid Sequence, Animals, Base Sequence, Cell Line, Cloning, Molecular, Enzyme Activation, Humans, Molecular Sequence Data, Phosphorylation, Protein-Tyrosine Kinases, Substrate Specificity, Transfection, Signal Transduction, Protein Serine-Threonine Kinases, Calcium-Calmodulin-Dependent Protein Kinases, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase Kinases, JNK Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, MAP Kinase Kinase 3, MAP Kinase Kinase 4

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Independent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms

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