ArticleMolecular biology of the cell2003
A new identity for MLK3 as an NIMA-related, cell cycle-regulated kinase that is localized near centrosomes and influences microtubule organization.
Article in Molecular biology of the cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 49 citations in OpenAlex.
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- Construction and experimental validation of a novel ferroptosis-related gene signature for myelodysplastic syndromes.Immunity, inflammation and disease · 2024Article
- Metastasis and MAPK Pathways.International journal of molecular sciences · 2022Review
- An ancestral recombination graph of human, Neanderthal, and Denisovan genomes.Science advances · 2021Article
- A subcellular map of the human kinome.eLife · 2021Article
- The regulatory function of mixed lineage kinase 3 in tumor and host immunity.Pharmacology & therapeutics · 2021Review
- MLK3 Signaling in Cancer Invasion.Cancers · 2016Review
- Mixed-lineage kinase 3 deficiency promotes neointima formation through increased activation of the RhoA pathway in vascular smooth muscle cells.Arteriosclerosis, thrombosis, and vascular biology · 2014Article
- MLK3 regulates fMLP-stimulated neutrophil motility.Molecular immunology · 2014Article
- Mixed Lineage Kinase-c-Jun N-Terminal Kinase Axis: A Potential Therapeutic Target in Cancer.Genes & cancer · 2013Review
- Mixed-lineage kinase 3 phosphorylates prolyl-isomerase Pin1 to regulate its nuclear translocation and cellular function.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Mixed lineage kinase 3 negatively regulates IKK activity and enhances etoposide-induced cell death.Biochimica et biophysica acta · 2009Article
- Mixed lineage kinase phosphorylates transcription factor E47 and inhibits TrkB expression to link neuronal death and survival pathways.The Journal of biological chemistry · 2009Article
- Cytokine-induced activation of mixed lineage kinase 3 requires TRAF2 and TRAF6.Cellular signalling · 2009Article
- MLK3 limits activated Galphaq signaling to Rho by binding to p63RhoGEF.Molecular cell · 2008Article
- Activation of c-Jun N-terminal kinase (JNK) by widely used specific p38 MAPK inhibitors SB202190 and SB203580: a MLK-3-MKK7-dependent mechanism.Cellular signalling · 2008Article
- Metabolic stress signaling mediated by mixed-lineage kinases.Molecular cell · 2007Article
- Mixed lineage kinases (MLKs): a role in dendritic cells, inflammation and immunity?International journal of experimental pathology · 2007Review
- Inhibition of mixed-lineage kinase (MLK) activity during G2-phase disrupts microtubule formation and mitotic progression in HeLa cells.Cellular signalling · 2006Article
- Role of MLK3 in the regulation of mitogen-activated protein kinase signaling cascades.Molecular and cellular biology · 2005Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
Although conserved counterparts for most proteins involved in the G(2)/M transition of the cell cycle have been found in all eukaryotes, a notable exception is the essential but functionally enigmatic fungal kinase NIMA. While a number of vertebrate kinases have been identified with catalytic domain homology to NIMA, none of these resemble NIMA within its extensive noncatalytic region, a region critical for NIMA function in Aspergillus nidulans. We used a bioinformatics approach to search for proteins with homology to the noncatalytic region of NIMA and identified mixed lineage kinase 3 (MLK3). MLK3 has been proposed to serve as a component in MAP kinase cascades, particularly those resulting in the activation of the c-Jun N-terminal kinase (JNK). Here we describe the first in-depth study of endogenous MLK3 and report that, like NIMA, MLK3 phosphorylation and activity are enhanced during G(2)/M, whereas JNK remains inactive. Coincident with the G(2)/M transition, a period marked by dramatic reorganization of the cytoplasmic microtubule network, endogenous MLK3 transiently disperses away from the centrosome and centrosomal-proximal sites where it is localized during interphase. Furthermore, when overexpressed, MLK3, like NIMA, localizes to the centrosomal region, induces profound disruption of cytoplasmic microtubules and a nuclear distortion phenotype that differs from mitotic chromosome condensation. Cellular depletion of MLK3 protein using siRNA technology results in an increased sensitivity to the microtubule-stabilizing agent taxol. Our studies suggest a new role for MLK3, separable from its function in the JNK pathway, that may contribute to promoting microtubule instability, a hallmark of M phase entry.
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