Journal ArticleDOI
From JNK to pay dirt: jun kinases, their biochemistry, physiology and clinical importance.
Michael Karin,Ewen Gallagher +1 more
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TLDR
The c‐Jun N‐terminal kinases (JNKs) were originally identified by their ability to phosphorylate c‐ Jun in response to UV‐irradiation, but now are recognized as critical regulators of various aspects of mammalian physiology, including: cell proliferation, cell survival, cell death, DNA repair and metabolism.Abstract:
The c-Jun N-terminal kinases (JNKs) were originally identified by their ability to phosphorylate c-Jun in response to UV-irradiation, but now are recognized as critical regulators of various aspects of mammalian physiology, including: cell proliferation, cell survival, cell death, DNA repair and metabolism JNK-mediated phosphorylation enhances the ability of c-Jun, a component of the AP-1 transcription factor, to activate transcription, in response to a plethora of extracellular stimuli The JNK activation leads to induction of AP-1-dependent target genes involved in cell proliferation, cell death, inflammation, and DNA repair The JNKs, which are encoded by three different Jnk loci, are now known to be regulated by many other stimuli, from pro-inflammatory cytokines to obesity, in addition to UV-irradiation Targeted disruption of the Jnk loci in mice has proved to be a critical tool in better understanding their physiological functions Such studies revealed that the JNKs play important roles in numerous cellular processes, including: programmed cell death, T cell differentiation, negative regulation of insulin signaling, control of fat deposition, and epithelial sheet migration Importantly, the JNKs have become prime targets for drug development in several important clinical areas, including: inflammation, diabetes, and cancerread more
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Signal integration by JNK and p38 MAPK pathways in cancer development
Erwin F. Wagner,Angel R. Nebreda +1 more
TL;DR: This Review highlights the recent progress made in defining the functions of the JNK and p38 MAPK pathways in different cancers.
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NF-κB activation by reactive oxygen species: Fifteen years later
TL;DR: This review critically review the recent data highlighting the role of ROS in NF-κB activation by proinflammatory cytokines (TNF-α and IL-1β) and lipopolysaccharide (LPS), two major components of innate immunity.
Journal ArticleDOI
Mammalian MAPK Signal Transduction Pathways Activated by Stress and Inflammation: A 10-Year Update
John M. Kyriakis,Joseph Avruch +1 more
TL;DR: The molecular components of the mammalian stress-regulated MAPK pathways and their regulation as described thus far are summarized and some of the in vivo functions of these pathways are reviewed.
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Innate immunity gone awry : linking microbial infections to chronic inflammation and cancer
TL;DR: How alteration of innate immune response genes in murine models can provide insights into the potential microbial origins of diverse conditions including Crohn's disease, psoriasis, atherosclerosis, diabetes, and liver cancer is reviewed.
Journal ArticleDOI
Endoplasmic reticulum stress responses.
TL;DR: This review summarizes how perturbation of three major functions of the endoplasmic reticulum in eukaryotic cells causes ER stress and activates signaling pathways collectively termed the unfolded protein response (UPR), and how the UPR reestablishes homeostasis.
References
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Journal ArticleDOI
Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.
Michael Karin,Yinon Ben-Neriah +1 more
TL;DR: Recent progress has been made in understanding the details of the signaling pathways that regulate NF-kappaB activity, particularly those responding to the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1.
Journal ArticleDOI
Signal transduction by the JNK group of MAP kinases.
TL;DR: This review will focus on the JNK group of MAP kinases, which are characterized by the sequence TEY and the two stress-activatedMAP kinases: p38 with the sequence TGY, and the c-Jun NH2-terminal kinases (JNK) with the sequences TPY.
Journal ArticleDOI
The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation.
Peter Angel,Michael Karin +1 more
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JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain
Benoit Dérijard,Benoit Dérijard,Masahiko Hibi,I-Huan Wu,I-Huan Wu,Tamera Barrett,Bing Su,Tiliang Deng,Michael Karin,Roger J. Davis,Roger J. Davis +10 more
TL;DR: JNK1 is a component of a novel signal transduction pathway that is activated by oncoproteins and UV irradiation and its properties indicate that JNK1 activation may play an important role in tumor promotion.
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A central role for JNK in obesity and insulin resistance
Jiro Hirosumi,Gurol Tuncman,Lufen Chang,Cem Z. Görgün,K. Teoman Uysal,Kazuhisa Maeda,Michael Karin,Gökhan S. Hotamisligil +7 more
TL;DR: It is shown that JNK activity is abnormally elevated in obesity and an absence of JNK1 results in decreased adiposity, significantly improved insulin sensitivity and enhanced insulin receptor signalling capacity in two different models of mouse obesity.