ArticleBlood2008
The Jak2V617F oncogene associated with myeloproliferative diseases requires a functional FERM domain for transformation and for expression of the Myc and Pim proto-oncogenes.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 133 citations in OpenAlex.
- Innovative strategies for mitochondrial dysfunction in myeloproliferative neoplasms a step toward precision medicine.Annals of medicine and surgery (2012) · 2025Review
- Pim Kinase Inhibition Disrupts CXCR4 Signalling in Megakaryocytes and Platelets by Reducing Receptor Availability at the Surface.International journal of molecular sciences · 2024Article
- Trisomy 8 Defines a Distinct Subtype of Myeloproliferative Neoplasms Driven by the MYC-Alarmin Axis.Blood cancer discovery · 2024Article
- Essential contribution of the JAK/STAT pathway to carcinogenesis, lytic infection of herpesviruses and pathogenesis of COVID‑19 (Review).Molecular medicine reports · 2024Review
- Pim Kinases: Important Regulators of Cardiovascular Disease.International journal of molecular sciences · 2023Review
- A novel IRAK4/PIM1 inhibitor ameliorates rheumatoid arthritis and lymphoid malignancy by blocking the TLR/MYD88-mediated NF-Acta pharmaceutica Sinica. B · 2023Article
- Circulating CD133+/–CD34– Have Increased c-Turkish journal of haematology : official journal of Turkish Society of Haematology · 2023Article
- Targeting Pim kinases in hematological cancers: molecular and clinical review.Molecular cancer · 2023Review
- Molecular Pathogenesis of Myeloproliferative Neoplasms.Current hematologic malignancy reports · 2022Review
- Review
- Article
- Small molecule inhibition of deubiquitinating enzyme JOSD1 as a novel targeted therapy for leukemias with mutant JAK2.Leukemia · 2022Article
- Review
- Proviral Integration of Moloney Virus-2 (PIM-2) Expression Level as a Prognostic Marker in Patients with Acute Myeloid Leukemia.International journal of general medicine · 2022Article
- Macrocyclization as a Source of Desired Polypharmacology. Discovery of Triple PI3K/mTOR/PIM Inhibitors.ACS medicinal chemistry letters · 2021Article
- MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies.Journal of hematology & oncology · 2021Review
- Review
- Article
- Review
- Janus kinase 2 activation mechanisms revealed by analysis of suppressing mutations.The Journal of allergy and clinical immunology · 2019Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
The V617F activating point mutation in Jak2 is associated with a proportion of myeloproliferative disorders. In normal hematopoietic cells, Jak2 signals only when associated with a growth factor receptor, such as the erythropoietin receptor (EpoR). We sought to identify the molecular requirements for activation of Jak2V617F by introducing a point mutation in the FERM domain (Y114A), required for receptor binding. Whereas BaF3.EpoR cells are readily transformed by Jak2V617F to Epo independence, we found that the addition of the FERM domain mutation blocked transformation and the induction of reactive oxygen species. Further, while cells expressing Jak2V617F had constitutive activation of STAT5, cells expressing Jak2V617F/Y114A did not, suggesting that signaling is defective at a very proximal level. In addition, expression of the Myc and Pim proto-oncogenes by Jak2V617F was found to be FERM domain dependent. An inducible constitutively active STAT5 mutant expressed in BaF3 cells was sufficient to induce Myc and Pim. Finally, the FERM domain in Jak2V617F was also required for abnormal hematopoiesis in transduced primary murine fetal liver cells. Overall, our results suggest that constitutive activation of Jak2 requires an intact FERM domain for a transforming phenotype, and is necessary for activation of the major target of Jak2, STAT5.
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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.