ArticleThe Journal of cell biology1999
Primary megakaryocytes reveal a role for transcription factor NF-E2 in integrin alpha IIb beta 3 signaling.
Article in The Journal of cell biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 81 citations in OpenAlex.
- Integrins and their role in megakaryocyte development and function.Experimental hematology · 2022Review
- Conditional CRISPR-mediated deletion of Lyn kinase enhances differentiation and function of iPSC-derived megakaryocytes.Journal of thrombosis and haemostasis : JTH · 2022Article
- Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications.International journal of molecular sciences · 2021Review
- RasGRP2 Structure, Function and Genetic Variants in Platelet Pathophysiology.International journal of molecular sciences · 2020Review
- SHARPIN at the nexus of integrin, immune, and inflammatory signaling in human platelets.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Site-specific phosphorylation regulates the functions of kindlin-3 in a variety of cells.Life science alliance · 2019Article
- Megakaryocytes compensate for Kit insufficiency in murine arthritis.The Journal of clinical investigation · 2017Article
- NF-E2, FLI1 and RUNX1 collaborate at areas of dynamic chromatin to activate transcription in mature mouse megakaryocytes.Scientific reports · 2016Article
- Review
- Regulation and function of the NFE2 transcription factor in hematopoietic and non-hematopoietic cells.Cellular and molecular life sciences : CMLS · 2015Review
- Rasa3 controls megakaryocyte Rap1 activation, integrin signaling and differentiation into proplatelet.PLoS genetics · 2014Article
- NF-E2 p45 is important for establishing normal function of platelets.Molecular and cellular biology · 2013Article
- Transcription factors in late megakaryopoiesis and related platelet disorders.Journal of thrombosis and haemostasis : JTH · 2013Review
- ACTN1 mutations cause congenital macrothrombocytopenia.American journal of human genetics · 2013Article
- Talin and signaling through integrins.Methods in molecular biology (Clifton, N.J.) · 2012Article
- Inhibitory effects of megakaryocytic cells in prostate cancer skeletal metastasis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2011Article
- Platelet formation.Seminars in hematology · 2010Review
- PAF-acetylhydrolase expressed during megakaryocyte differentiation inactivates PAF-like lipids.Blood · 2009Article
- Dynamin 3 participates in the growth and development of megakaryocytes.Experimental hematology · 2008Article
- Characterization of calcium- and integrin-binding protein 1 (CIB1) knockout platelets: potential compensation by CIB family members.Thrombosis and haemostasis · 2008Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Platelet integrin alphaIIbbeta3 responds to intracellular signals by binding fibrinogen and triggering cytoskeletal reorganization, but the mechanisms of alphaIIbbeta3 signaling remain poorly understood. To better understand this process, we established conditions to study alphaIIbbeta3 signaling in primary murine megakaryocytes. Unlike platelets, these platelet precursors are amenable to genetic manipulation. Cytokine-stimulated bone marrow cultures produced three arbitrary populations of alphaIIbbeta3-expressing cells with increasing size and DNA ploidy: small progenitors, intermediate-size young megakaryocytes, and large mature megakaryocytes. A majority of the large megakaryocytes bound fibrinogen in response to agonists, while almost none of the smaller cells did. Fibrinogen binding to large megakaryocytes was inhibited by Sindbis virus-mediated expression of isolated beta3 integrin cytoplasmic tails. Strikingly, large megakaryocytes from mice deficient in the transcription factor NF-E2 failed to bind fibrinogen in response to agonists, despite normal surface expression of alphaIIbbeta3. Furthermore, while megakaryocytes from wild-type mice spread on immobilized fibrinogen and exhibited filopodia, lamellipodia and Rho-dependent focal adhesions and stress fibers, NF-E2-deficient megakaryocytes adhered poorly. These studies establish that agonist-induced activation of alphaIIbbeta3 is controlled by NF-E2-regulated signaling pathways that mature late in megakaryocyte development and converge at the beta3 cytoplasmic tail. Megakaryocytes provide a physiologically relevant and tractable system for analysis of bidirectional alphaIIbbeta3 signaling.
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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.