Two ubiquitously expressed isoforms of c-Jun N-terminal protein kinase (JNK), JNK1 and JNK2, have shared functions and different functions. However, the molecular mechanism is unknown. Here we report that JNK1, but not JNK2, is essential for tumor necrosis factor alpha (TNF-alpha)-induced c-Jun kinase activation, c-Jun expression, and apoptosis. Using mouse fibroblasts deficient in either Jnk1 or Jnk2, we found that JNK1 was activated by TNF-alpha, whereas JNK2 activation was negligible. In addition, JNK2 interfered with JNK1 activation via its "futile" phosphorylation by upstream kinases. Consequently, expression and activation of c-Jun, which depends on JNK activity, were impaired in Jnk1 null cells but enhanced in Jnk2 null cells. TNF-alpha-induced apoptosis was also suppressed in Jnk1 null fibroblasts but increased in Jnk2 null cells. Thus, our results provide a molecular mechanism underlying the different biological functions of JNK isoforms.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC533995 | PMC |
| http://dx.doi.org/10.1128/MCB.24.24.10844-10856.2004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Inhibition of JNK signaling attenuates photoreceptor ferroptosis caused by all-trans-retinal.
Free Radic Biol Med
December 2024
Department of Ophthalmology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361003, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Fujian Engineering and Research Center of Eye Regenerative Medicine, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Shenzhen Research Institute of Xiamen University, Shenzhen, Guangdong, 518057, China. Electronic address:
The disruption of the visual cycle leads to the accumulation of all-trans-retinal (atRAL) in the retina, a hallmark of autosomal recessive Stargardt disease (STGD1) and dry age-related macular degeneration (AMD), both of which cause retinal degeneration. Although our previous studies have shown that atRAL induces ferroptosis and activates c-Jun N-terminal kinase (JNK) signaling in the retina, the relationship between JNK signaling and ferroptosis in atRAL-mediated photoreceptor damage remains unclear. Here, we reported that JNK activation by atRAL drove photoreceptor ferroptosis through ferritinophagy.
View Article and Find Full Text PDFA focus on c-Jun-N-terminal kinase signaling in sepsis-associated multiple organ dysfunction: Mechanisms and therapeutic strategies.
Int Immunopharmacol
December 2024
Laboratory of Neuroendocrinology, Department of Pharmacology, Central University of Punjab, Ghudda, Bathinda, India. Electronic address:
Sepsis is a life-threatening condition characterized by a widespread inflammatory response to infection, inevitably leading to multiple organ dysfunctions. Extensive research, both in vivo and in vitro, has revealed key factors contributing to sepsis, such as apoptosis, inflammation, cytokine release, oxidative stress, and systemic stress. The changes observed during sepsis-induced conditions are mainly attributed to altered signal transduction pathways, which play a critical role in cell proliferation, migration, and apoptosis.
View Article and Find Full Text PDFHydrogen sulfide ameliorated endothelial dysfunction in hyperhomocysteinemia rats: Mechanism of IRE1α/JNK pathway-mediated autophagy.
Nitric Oxide
December 2024
Department of Physiology, Institute of Basic Medicine, Hebei Medical University, 050017, Hebei, China; Hebei Key Laboratory of Cardiovascular Homeostasis and Aging, 050017, Hebei, China; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, 050017, Hebei, China; Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease, 050017, Hebei, China. Electronic address:
Previous studies showed that hyperhomocysteinemia (HHcy) induced endothelial dysfunction by endoplasmic reticulum (ER) stress induction and autophagy stimulation. This study aimed to determine the effect of hydrogen sulfide (HS) in homocysteine (Hcy)-induced endothelial dysfunction and observe the possible mechanism involved. Male Wistar rats (160-180g) were used and randomly divided into four groups: Control group, HHcy group, HHcy+Sodium hydrosulfide (NaHS) group and NaHS group.
View Article and Find Full Text PDFAlda-1 attenuation of binge alcohol-caused atrial arrhythmias through a novel mechanism of suppressed c-Jun N-terminal Kinase-2 activity.
J Mol Cell Cardiol
December 2024
Department of Physiology and Cell Biology, College of Medicine/Wexner Medical Center, The Ohio State University, Columbus, OH, USA. Electronic address:
Article Synopsis
- Holiday Heart Syndrome (HHS) is linked to excessive binge drinking, resulting in atrial fibrillation (AF), which poses significant health risks and is of great concern for prevention and treatment.
- This study explores the beneficial effects of Alda-1, which counteracts alcohol-induced calcium (Ca) abnormalities and arrhythmias in mouse atria and isolated human heart channels, suggesting a protective role in HHS-related AF.
- Findings reveal that Alda-1 inhibits JNK2 enzyme activity independently of alcohol detoxification pathways, providing insights into a potential therapeutic approach to reduce binge alcohol-related arrhythmogenic effects.
Inactivation of JNK signalling results in polarity loss and cell senescence of Sertoli cell.
Cell Prolif
September 2024
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Article Synopsis
- Sertoli cells in the testis are crucial for male reproductive health, and their proper development is influenced by various factors, including JNK signaling.
- Disruption of JNK signaling through the double knockout of Jnk1 and Jnk2 leads to misplaced Sertoli cells during early development and their eventual loss, indicating its importance in cell localization and survival.
- The study suggests that JNK signaling is vital for maintaining Sertoli cell polarity and function, and its disruption may be linked to male infertility due to cellular senescence and proteolysis issues.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!