Cited by 3,188Protein Kinase Regulation and GTPase SignalingMelanoma and MAPK PathwaysNF-κB Signaling Pathways

JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain

Dérijard, Benoit, Hibi, Masahiko, Wu, I-Huan, Barrett, Tamera, Su, Bing, Deng, Tiliang, Karin, Michael, Davis, Roger J.·1994·Cell

Abstract

The ultraviolet (UV) response of mammalian cells is characterized by a rapid and selective increase in gene expression mediated by AP-1 and NF-kappa B. The effect on AP-1 transcriptional activity results, in part, from enhanced phosphorylation of the c-Jun NH2-terminal activation domain. Here, we describe the molecular cloning and characterization of JNK1, a distant relative of the MAP kinase group that is activated by dual phosphorylation at Thr and Tyr during the UV response. Significantly, Ha-Ras partially activates JNK1 and potentiates the activation caused by UV. JNK1 binds to the c-Jun transactivation domain and phosphorylates it on Ser-63 and Ser-73. Thus, JNK1 is a component of a novel signal transduction pathway that is activated by oncoproteins and UV irradiation. These properties indicate that JNK1 activation may play an important role in tumor promotion.

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Crossref · 10.1016/0092-8674(94)90380-8

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Authors
Dérijard, B., Hibi, M., Wu, I.-H., Barrett, T., Su, B., Deng, T., Karin, M., & Davis, R. J.
Affiliations
  • Howard Hughes Medical Institute (US)
  • University of Massachusetts Chan Medical School (US)
Venue
Cell
Publisher
Elsevier BV
Published
1994-03
Volume
76
Issue
6
Pages
1025-1037
ISSN
0092-8674 (ISSN-L)
OpenAlex
W1984903682
Cited by
3,188
References
59
Citations by year
2026: 16 · 2025: 16 · 2024: 22 · 2023: 13 · 2022: 22 · 2021: 17 · 2020: 25 · 2019: 28 · 2018: 30 · 2017: 36 · 2016: 36 · 2015: 48 · 2014: 47 · 2013: 63 · 2012: 58
FWCI
92.64
Type
journal article
Language
en
Open access
closed
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01gm037845-08, 5r01ca058396-09, 5p01ca050528-07)
  • National Cancer Institute (CA 58396, CA50528)
  • National Institute of General Medical Sciences (GM37845)
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 › Cancer Research › NF-κB Signaling Pathways
Keywords
JNK1, c-Jun N-terminal kinase, ultraviolet response, Ha-ras, mitogen-activated protein kinase, AP-1 transcription, signal transduction, tumor promotion, oncoprotein, dual phosphorylation
MeSH terms
Amino Acid Sequence, Base Sequence, Binding Sites, Cell Line, Enzyme Activation, Humans, Molecular Sequence Data, Phosphorylation, Protein Binding, Substrate Specificity, Ultraviolet Rays, Transcriptional Activation, Oncogene Protein p21(ras), Proto-Oncogene Proteins c-jun, Protein Serine-Threonine Kinases, Sequence Homology, Amino Acid, Calcium-Calmodulin-Dependent Protein Kinases, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases

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