ArticleMolecular and cellular biology2001
The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosis.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 267 citations in OpenAlex.
- Remyelination protects neurons from DLK-mediated neurodegeneration.Nature communications · 2024Article
- Remyelination protects neurons from DLK-mediated neurodegeneration.bioRxiv : the preprint server for biology · 2024Article
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- Parkinson's disease models and death signaling: what do we know until now?Frontiers in neuroanatomy · 2024Review
- Stress-induced vesicular assemblies of dual leucine zipper kinase are signaling hubs involved in kinase activation and neurodegeneration.The EMBO journal · 2022Article
- Inactivating Celsr2 promotes motor axon fasciculation and regeneration in mouse and human.Brain : a journal of neurology · 2022Article
- Peroxynitrite nitration of Tyr 56 in Hsp90 induces PC12 cell death through P2X7R-dependent PTEN activation.Redox biology · 2022Article
- LATS1 Regulates Mixed-Lineage Kinase 3 (MLK3) Subcellular Localization and MLK3-Mediated Invasion in Ovarian Epithelial Cells.Molecular and cellular biology · 2021Article
- The regulatory function of mixed lineage kinase 3 in tumor and host immunity.Pharmacology & therapeutics · 2021Review
- Different Gene Networks Are Disturbed by Zika Virus Infection in A Mouse Microcephaly Model.Genomics, proteomics & bioinformatics · 2020Article
- Dual Leucine Zipper Kinase Is Constitutively Active in the Adult Mouse Brain and Has Both Stress-Induced and Homeostatic Functions.International journal of molecular sciences · 2020Article
- circ-016910 sponges miR-574-5p to regulate cell physiology and milk synthesis via MAPK and PI3K/AKT-mTOR pathways in GMECs.Journal of cellular physiology · 2020Article
- Review
- Apoptotic cell death regulation in neurons.The FEBS journal · 2019Review
- Article
- Broad Spectrum Mixed Lineage Kinase Type 3 Inhibition and HIV-1 Persistence in Macrophages.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019Review
- Apoptosis versus axon pruning: Molecular intersection of two distinct pathways for axon degeneration.Neuroscience research · 2019Review
- Oncogenic activation of PI3K induces progenitor cell differentiation to suppress epidermal growth.Nature cell biology · 2018Article
- The tumor suppressor role of miR-155-5p in gastric cancer.Oncology letters · 2018Article
- URMC-099 facilitates amyloid-β clearance in a murine model of Alzheimer's disease.Journal of neuroinflammation · 2018Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuronal apoptotic death induced by nerve growth factor (NGF) deprivation is reported to be in part mediated through a pathway that includes Rac1 and Cdc42, mitogen-activated protein kinase kinases 4 and 7 (MKK4 and -7), c-Jun N-terminal kinases (JNKs), and c-Jun. However, additional components of the pathway remain to be defined. We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling. Overexpression of MLKs effectively induces apoptotic death of cultured neuronal PC12 cells and sympathetic neurons, while expression of dominant-negative forms of MLKs suppresses death evoked by NGF deprivation or expression of activated forms of Rac1 and Cdc42. CEP-1347 (KT7515), which blocks neuronal death caused by NGF deprivation and a variety of additional apoptotic stimuli and which selectively inhibits the activities of MLKs, effectively protects neuronal PC12 cells from death induced by overexpression of MLK family members. In addition, NGF deprivation or UV irradiation leads to an increase in both level and phosphorylation of endogenous DLK. These observations support a role for MLKs in the neuronal death mechanism. With respect to ordering the death pathway, dominant-negative forms of MKK4 and -7 and c-Jun are protective against death induced by MLK overexpression, placing MLKs upstream of these kinases. Additional findings place the MLKs upstream of mitochondrial cytochrome c release and caspase activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.