ArticleThe Journal of clinical investigation2018
Thrombocytopenia-associated mutations in Ser/Thr kinase MASTL deregulate actin cytoskeletal dynamics in platelets.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- The impact of a high fat diet and platelet activation on pre-metastatic niche formation.Nature communications · 2025Article
- [Newly diagnosed non-acute promyelocytic leukemia combined with disseminated intravascular coagulation: a case report and literature review].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2024Review
- IL-22 regulates MASTL expression in intestinal epithelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Review
- SILAC kinase screen identifies potential MASTL substrates.Scientific reports · 2022Article
- Comparison of the central human and mouse platelet signaling cascade by systems biological analysis.BMC genomics · 2020Article
- PP2A-B55 Holoenzyme Regulation and Cancer.Biomolecules · 2020Review
- Inherited thrombocytopenias: history, advances and perspectives.Haematologica · 2020Review
- Review
- Genetic colocalization atlas points to common regulatory sites and genes for hematopoietic traits and hematopoietic contributions to disease phenotypes.BMC medical genomics · 2020Article
- MASTL promotes cell contractility and motility through kinase-independent signaling.The Journal of cell biology · 2020Article
- C3G contributes to platelet activation and aggregation by regulating major signaling pathways.Signal transduction and targeted therapy · 2020Article
- Article
- Molecular Basis of the Mechanisms Controlling MASTL.Molecular & cellular proteomics : MCP · 2020Article
- Inherited Thrombocytopenia: Update on Genes and Genetic Variants Which may be Associated With Bleeding.Frontiers in cardiovascular medicine · 2019Review
- The Oncogenic Functions of MASTL Kinase.Frontiers in cell and developmental biology · 2018Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
MASTL, a Ser/Thr kinase that inhibits PP2A-B55 complexes during mitosis, is mutated in autosomal dominant thrombocytopenia. However, the connections between the cell-cycle machinery and this human disease remain unexplored. We report here that, whereas Mastl ablation in megakaryocytes prevented proper maturation of these cells, mice carrying the thrombocytopenia-associated mutation developed thrombocytopenia as a consequence of aberrant activation and survival of platelets. Activation of mutant platelets was characterized by hyperstabilized pseudopods mimicking the effect of PP2A inhibition and actin polymerization defects. These aberrations were accompanied by abnormal hyperphosphorylation of multiple components of the actin cytoskeleton and were rescued both in vitro and in vivo by inhibiting upstream kinases such as PKA, PKC, or AMPK. These data reveal an unexpected role of Mastl in actin cytoskeletal dynamics in postmitotic cells and suggest that the thrombocytopenia-associated mutation in MASTL is a pathogenic dominant mutation that mimics decreased PP2A activity resulting in altered phosphorylation of cytoskeletal regulatory pathways.
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