ArticleNature communications2017
Membrane-binding and activation of LKB1 by phosphatidic acid is essential for development and tumour suppression.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 50 citations in OpenAlex.
- Illuminating compartmentalized AMPK signaling in single cells.The Biochemical journal · 2026Review
- Synthetic Lipid Biology.Chemical reviews · 2025Review
- Shear stress-stimulated AMPK couples endothelial cell mechanics, metabolism and vasodilation.Journal of cell science · 2024Article
- Phosphatidic acid directly activates mTOR and then regulates SREBP to promote ganoderic acid biosynthesis under heat stress in Ganoderma lingzhi.Communications biology · 2024Article
- LKB1 biology: assessing the therapeutic relevancy of LKB1 inhibitors.Cell communication and signaling : CCS · 2024Review
- Mechanical activation of VE-cadherin stimulates AMPK to increase endothelial cell metabolism and vasodilation.bioRxiv : the preprint server for biology · 2024Article
- Elucidating the Membrane Binding Process of a Disordered Protein: Dynamic Interplay of Anionic Lipids and the Polybasic Region.ACS physical chemistry Au · 2024Article
- Ultralow Background Membrane Editors for Spatiotemporal Control of Phosphatidic Acid Metabolism and Signaling.ACS central science · 2024Article
- The exocyst complex and intracellular vesicles mediate soluble protein trafficking to the primary cilium.Communications biology · 2024Article
- Endocannabinoid biosynthetic enzymes regulate pain response via LKB1-AMPK signaling.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- LKB1-SIK2 loss drives uveal melanoma proliferation and hypersensitivity to SLC8A1 and ROS inhibition.EMBO molecular medicine · 2023Article
- Ultralow background membrane editors for spatiotemporal control of lipid metabolism and signaling.bioRxiv : the preprint server for biology · 2023Article
- LKB1 signaling is altered in skeletal muscle of a Duchenne muscular dystrophy mouse model.Disease models & mechanisms · 2023Article
- Activity-based directed evolution of a membrane editor in mammalian cells.Nature chemistry · 2023Article
- Article
- Upregulated phospholipase D2 expression and activity is related to the metastatic properties of melanoma.Oncology letters · 2022Article
- PIM kinases inhibit AMPK activation and promote tumorigenicity by phosphorylating LKB1.Cell communication and signaling : CCS · 2021Article
- Adenosine A2A receptor signaling promotes FoxO associated autophagy in chondrocytes.Scientific reports · 2021Article
- The diversity and breadth of cancer cell fatty acid metabolism.Cancer & metabolism · 2021Review
- The long noncoding RNA CRAL reverses cisplatin resistance via the miR-505/CYLD/AKT axis in human gastric cancer cells.RNA biology · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serine/threonine kinase LKB1 regulates various cellular processes such as cell proliferation, energy homeostasis and cell polarity and is frequently downregulated in various tumours. Many downstream pathways controlled by LKB1 have been described but little is known about the upstream regulatory mechanisms. Here we show that targeting of the kinase to the membrane by a direct binding of LKB1 to phosphatidic acid is essential to fully activate its kinase activity. Consequently, LKB1 mutants that are deficient for membrane binding fail to activate the downstream target AMPK to control mTOR signalling. Furthermore, the in vivo function of LKB1 during development of Drosophila depends on its capacity to associate with membranes. Strikingly, we find LKB1 to be downregulated in malignant melanoma, which exhibit aberrant activation of Akt and overexpress phosphatidic acid generating Phospholipase D. These results provide evidence for a fundamental mechanism of LKB1 activation and its implication in vivo and during carcinogenesis.
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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.