ArticleGenes & development2012
A Src family kinase-Shp2 axis controls RUNX1 activity in megakaryocyte and T-lymphocyte differentiation.
Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 66 citations in OpenAlex.
- Epigenetic programming by H3K23ac defines lineage fate of Meg3Nature cell biology · 2026Article
- Phosphorylation of Runx protein controls helper CD4Nature immunology · 2026Article
- VHL synthetic lethality screens uncover CBF-β as a negative regulator of STING.Nature communications · 2026Article
- Elucidation of the Roles of CD22 Cis-Ligands in B Lymphocyte Development and Signaling Using Genetic and Chemical Tools.Advances in experimental medicine and biology · 2026Review
- Innate immune mechanisms hijacked by leukemia-initiating stem cells for selective advantage and immune evasion in Ptpn11-associated JMML.Cell reports · 2025Article
- Anti-lymphoma peptide is inspired by mapping a sequence of four amino acids of KRAI motif as nuclear localization signal of Crlz-1.Molecular therapy. Oncology · 2025Article
- RUNX1 isoforms regulate RUNX1 and target genes differentially in platelets-megakaryocytes: association with clinical cardiovascular events.Journal of thrombosis and haemostasis : JTH · 2024Article
- RUNX1 Isoforms Regulate RUNX1 and Target-Genes Differentially in Platelets-Megakaryocytes: Association with Clinical Cardiovascular Events.bioRxiv : the preprint server for biology · 2024Article
- Article
- SHP2 inhibitors maintain TGFβ signalling through SMURF2 inhibition.NPJ precision oncology · 2023Article
- Runx1-R188Q germ line mutation induces inflammation and predisposition to hematologic malignancies in mice.Blood advances · 2023Article
- Article
- miR-23a-3p Regulates Runx2 to Inhibit the Proliferation and Metastasis of Oral Squamous Cell Carcinoma.Journal of oncology · 2022Article
- Targeted Ptpn11 deletion in mice reveals the essential role of SHP2 in osteoblast differentiation and skeletal homeostasis.Bone research · 2021Article
- Comprehensive Analysis of RUNX and TGF-β Mediated Regulation of Immune Cell Infiltration in Breast Cancer.Frontiers in cell and developmental biology · 2021Article
- Identification and Targeting of Thomsen-Friedenreich and IL1RAP Antigens on Chronic Myeloid Leukemia Stem Cells Using Bi-Specific Antibodies.OncoTargets and therapy · 2021Article
- RUNX1: an emerging therapeutic target for cardiovascular disease.Cardiovascular research · 2020Review
- RUNX1 Dosage in Development and Cancer.Molecules and cells · 2020Review
- Poly(C)-Binding Protein Pcbp2 Enables Differentiation of Definitive Erythropoiesis by Directing Functional Splicing of the Runx1 Transcript.Molecular and cellular biology · 2018Article
- Mathematical Analysis of Cytokine-Induced Differentiation of Granulocyte-Monocyte Progenitor Cells.Frontiers in immunology · 2018Article
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9 authors at 4 institutions in 1 country.
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Abstract
Hematopoietic development occurs in complex microenvironments and is influenced by key signaling events. Yet how these pathways communicate with master hematopoietic transcription factors to coordinate differentiation remains incompletely understood. The transcription factor RUNX1 plays essential roles in definitive hematopoietic stem cell (HSC) ontogeny, HSC maintenance, megakaryocyte (Mk) maturation, and lymphocyte differentiation. It is also the most frequent target of genetic alterations in human leukemia. Here, we report that RUNX1 is phosphorylated by Src family kinases (SFKs) and that this occurs on multiple tyrosine residues located within its negative regulatory DNA-binding and autoinhibitory domains. Retroviral transduction, chemical inhibitor, and genetic studies demonstrate a negative regulatory role of tyrosine phosphorylation on RUNX1 activity in Mk and CD8 T-cell differentiation. We also demonstrate that the nonreceptor tyrosine phosphatase Shp2 binds directly to RUNX1 and contributes to its dephosphorylation. Last, we show that RUNX1 tyrosine phosphorylation correlates with reduced GATA1 and enhanced SWI/SNF interactions. These findings link SFK and Shp2 signaling pathways to the regulation of RUNX1 activity in hematopoiesis via control of RUNX1 multiprotein complex assembly.
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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.