Regulation of the Activity of the Dual Leucine Zipper Kinase by Distinct Mechanisms
The dual leucine zipper kinase (DLK) alias mitogen-activated protein 3 kinase 12 (MAP3K12) has gained much attention in recent years. DLK belongs to the mixed lineage kinases, characterized by homology to serine/threonine and tyrosine kinase, but exerts serine/threonine kinase activity. DLK has been...
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MDPI AG
2024-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/4/333 |
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| author | Kyra-Alexandra Köster Marten Dethlefs Jorge Duque Escobar Elke Oetjen |
| author_facet | Kyra-Alexandra Köster Marten Dethlefs Jorge Duque Escobar Elke Oetjen |
| author_sort | Kyra-Alexandra Köster |
| collection | DOAJ |
| description | The dual leucine zipper kinase (DLK) alias mitogen-activated protein 3 kinase 12 (MAP3K12) has gained much attention in recent years. DLK belongs to the mixed lineage kinases, characterized by homology to serine/threonine and tyrosine kinase, but exerts serine/threonine kinase activity. DLK has been implicated in many diseases, including several neurodegenerative diseases, glaucoma, and diabetes mellitus. As a MAP3K, it is generally assumed that DLK becomes phosphorylated and activated by upstream signals and phosphorylates and activates itself, the downstream serine/threonine MAP2K, and, ultimately, MAPK. In addition, other mechanisms such as protein–protein interactions, proteasomal degradation, dephosphorylation by various phosphatases, palmitoylation, and subcellular localization have been shown to be involved in the regulation of DLK activity or its fine-tuning. In the present review, the diverse mechanisms regulating DLK activity will be summarized to provide better insights into DLK action and, possibly, new targets to modulate DLK function. |
| first_indexed | 2024-03-07T22:38:09Z |
| format | Article |
| id | doaj.art-e1ce1ad77a894886b5f20b2834e04279 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-07T22:38:09Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj.art-e1ce1ad77a894886b5f20b2834e042792024-02-23T15:11:55ZengMDPI AGCells2073-44092024-02-0113433310.3390/cells13040333Regulation of the Activity of the Dual Leucine Zipper Kinase by Distinct MechanismsKyra-Alexandra Köster0Marten Dethlefs1Jorge Duque Escobar2Elke Oetjen3Department of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, GermanyDZHK Standort Hamburg, Kiel, Lübeck, GermanyDepartment of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, GermanyThe dual leucine zipper kinase (DLK) alias mitogen-activated protein 3 kinase 12 (MAP3K12) has gained much attention in recent years. DLK belongs to the mixed lineage kinases, characterized by homology to serine/threonine and tyrosine kinase, but exerts serine/threonine kinase activity. DLK has been implicated in many diseases, including several neurodegenerative diseases, glaucoma, and diabetes mellitus. As a MAP3K, it is generally assumed that DLK becomes phosphorylated and activated by upstream signals and phosphorylates and activates itself, the downstream serine/threonine MAP2K, and, ultimately, MAPK. In addition, other mechanisms such as protein–protein interactions, proteasomal degradation, dephosphorylation by various phosphatases, palmitoylation, and subcellular localization have been shown to be involved in the regulation of DLK activity or its fine-tuning. In the present review, the diverse mechanisms regulating DLK activity will be summarized to provide better insights into DLK action and, possibly, new targets to modulate DLK function.https://www.mdpi.com/2073-4409/13/4/333dual leucine zipper kinasephosphorylationprotein–protein interactionproteasomal degradationpalmitoylation |
| spellingShingle | Kyra-Alexandra Köster Marten Dethlefs Jorge Duque Escobar Elke Oetjen Regulation of the Activity of the Dual Leucine Zipper Kinase by Distinct Mechanisms Cells dual leucine zipper kinase phosphorylation protein–protein interaction proteasomal degradation palmitoylation |
| title | Regulation of the Activity of the Dual Leucine Zipper Kinase by Distinct Mechanisms |
| title_full | Regulation of the Activity of the Dual Leucine Zipper Kinase by Distinct Mechanisms |
| title_fullStr | Regulation of the Activity of the Dual Leucine Zipper Kinase by Distinct Mechanisms |
| title_full_unstemmed | Regulation of the Activity of the Dual Leucine Zipper Kinase by Distinct Mechanisms |
| title_short | Regulation of the Activity of the Dual Leucine Zipper Kinase by Distinct Mechanisms |
| title_sort | regulation of the activity of the dual leucine zipper kinase by distinct mechanisms |
| topic | dual leucine zipper kinase phosphorylation protein–protein interaction proteasomal degradation palmitoylation |
| url | https://www.mdpi.com/2073-4409/13/4/333 |
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