ArticleThe Journal of biological chemistry2010
Protein phosphatase 2A (PP2A) holoenzymes regulate death-associated protein kinase (DAPK) in ceramide-induced anoikis.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 51 citations in OpenAlex.
- The Emerging Role of the Cancerous Inhibitor of Protein Phosphatase 2A in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2025Review
- Role of Protein Phosphatases in Tumor Angiogenesis: Assessing PP1, PP2A, PP2B and PTPs Activity.International journal of molecular sciences · 2024Review
- Death-associated protein kinase 1 as a therapeutic target for Alzheimer's disease.Translational neurodegeneration · 2024Review
- Dihydroceramide desaturase 1 (DES1) promotes anchorage-independent survival downstream of HER2-driven glucose uptake and metabolism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Phase I Targeted Combination Trial of Sorafenib and GW5074 in Patients with Advanced Refractory Solid Tumors.Journal of clinical medicine · 2022Article
- The Synergistic Cytotoxic Effects of GW5074 and Sorafenib by Impacting Mitochondrial Functions in Human Colorectal Cancer Cell Lines.Frontiers in oncology · 2022Article
- Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance.Molecular oncology · 2021Review
- Inorganic Phosphate (Pi) Signaling in Endothelial Cells: A Molecular Basis for Generation of Endothelial Microvesicles in Uraemic Cardiovascular Disease.International journal of molecular sciences · 2020Article
- Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease.International journal of molecular sciences · 2019Review
- Transposon mutagenesis screen in mice identifies TM9SF2 as a novel colorectal cancer oncogene.Scientific reports · 2018Article
- Lipids in the cell: organisation regulates function.Cellular and molecular life sciences : CMLS · 2018Review
- Article
- Death-associated protein kinase 1 phosphorylates NDRG2 and induces neuronal cell death.Cell death and differentiation · 2017Article
- TheFrontiers in microbiology · 2017Article
- Death Associated Protein Kinase 1 (DAPK1): A Regulator of Apoptosis and Autophagy.Frontiers in molecular neuroscience · 2016Review
- Review
- Lysosomal degradation of CD44 mediates ceramide nanoliposome-induced anoikis and diminished extravasation in metastatic carcinoma cells.The Journal of biological chemistry · 2015Article
- Control of autophagy maturation by acid sphingomyelinase in mouse coronary arterial smooth muscle cells: protective role in atherosclerosis.Journal of molecular medicine (Berlin, Germany) · 2014Article
- Self-consumption: the interplay of autophagy and apoptosis.Nature reviews. Molecular cell biology · 2014Review
- Early activation of nSMase2/ceramide pathway in astrocytes is involved in ischemia-associated neuronal damage via inflammation in rat hippocampi.Journal of neuroinflammation · 2013Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The tumor suppressor, death-associated protein kinase (DAPK), is a Ca(2+)/calmodulin-regulated Ser/Thr kinase with an important role in regulating cytoskeletal dynamics. Autophosphorylation within the calmodulin-binding domain at Ser-308 inhibits DAPK catalytic activity. Dephosphorylation of Ser-308 by a previously unknown phosphatase enhances kinase activity and proteasome-mediated degradation of DAPK. In these studies, we identified two holoenzyme forms of protein phosphatase 2A (PP2A), ABalphaC and ABdeltaC, as DAPK-interacting proteins. These phosphatase holoenzymes dephosphorylate DAPK at Ser-308 in vitro and in vivo resulting in enhanced kinase activity of DAPK. The enzymatic activity of PP2A also negatively regulates DAPK levels by enhancing proteasome-mediated degradation of the kinase. Overexpression of wild type DAPK induces cell rounding and detachment in HEK293 cells; however, this effect is not observed following expression of an inactive DAPK S308E mutant. Finally, activation of DAPK by PP2A was found to be required for ceramide-induced anoikis. Together, our results provide a mechanism by which PP2A and DAPK activities control cell adhesion and anoikis.
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Registered trials
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.