ArticleThe Journal of biological chemistry2012
Suppressor of cytokine signaling 6 (SOCS6) negatively regulates Flt3 signal transduction through direct binding to phosphorylated tyrosines 591 and 919 of Flt3.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 82 citations in OpenAlex.
- Article
- Review
- SOCS Proteins: Key Players in Immune Regulation During SARS-CoV-2 Infection.European journal of immunology · 2025Review
- The Neglected Suppressor of Cytokine Signalling (SOCS): SOCS4-7.Inflammation · 2025Review
- MiR-568-5p, the key regulator of suppressor of cytokine signaling 4 (SOCS4) in the coronary artery disease.Journal of diabetes and metabolic disorders · 2025Article
- Importance of PTM of FLT3 in acute myeloid leukemia.Acta biochimica et biophysica Sinica · 2024Review
- BRCC36 associates with FLT3-ITD to regulate its protein stability and intracellular signaling in acute myeloid leukemia.Cancer science · 2024Article
- Unravelling the druggability and immunological roles of the SOCS-family proteins.Frontiers in immunology · 2024Review
- TET2-mediated mRNA demethylation regulates leukemia stem cell homing and self-renewal.Cell stem cell · 2023Article
- Role of SOCS and VHL Proteins in Neuronal Differentiation and Development.International journal of molecular sciences · 2023Review
- A Receptor Tyrosine Kinase Inhibitor Sensitivity Prediction Model Identifies AXL Dependency in Leukemia.International journal of molecular sciences · 2023Article
- Regulation of mi-RNAs Target Cancer Genes Between Exercise and Non-exercise in Rat Rheumatoid Arthritis Induction: Pilot Study.Epigenetics insights · 2022Article
- Down-regulation of SOCS6: an unfavorable prognostic factor for gastrointestinal stromal tumor proven by survival analysis.Diagnostic pathology · 2021Article
- The Emerging Role of Suppressors of Cytokine Signaling (SOCS) in the Development and Progression of Leukemia.Cancers · 2021Review
- Article
- RNA Sequencing Reveals Distinct Immune Responses in the Chorioamniotic Membranes of Women with Preterm Labor and Microbial or Sterile Intra-amniotic Inflammation.Infection and immunity · 2021Article
- SOCS6 promotes radiosensitivity and decreases cancer cell stemness in esophageal squamous cell carcinoma by regulating c-Kit ubiquitylation.Cancer cell international · 2021Article
- Phosphorylation regulates cullin-based ubiquitination in tumorigenesis.Acta pharmaceutica Sinica. B · 2021Review
- Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFβ Pathway.International journal of molecular sciences · 2020Article
- Megakaryocytic Expansion in Gilteritinib-Treated Acute Myeloid Leukemia Patients Is Associated With AXL Inhibition.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The receptor tyrosine kinase Flt3 is an important growth factor receptor in hematopoiesis, and gain-of-function mutations of the receptor contribute to the transformation of acute myeloid leukemia. SOCS6 (suppressor of cytokine signaling 6) is a member of the SOCS family of E3 ubiquitin ligases that can regulate receptor tyrosine kinase signal transduction. In this study, we analyzed the role of SOCS6 in Flt3 signal transduction. The results show that ligand stimulation of Flt3 can induce association of SOCS6 and Flt3 and tyrosine phosphorylation of SOCS6. Phosphopeptide fishing indicated that SOCS6 binds directly to phosphotyrosines 591 and 919 of Flt3. By using stably transfected Ba/F3 cells with Flt3 and/or SOCS6, we show that the presence of SOCS6 can enhance ubiquitination of Flt3, as well as internalization and degradation of the receptor. The presence of SOCS6 also induces weaker activation of Erk1/2, but not Akt, in transfected Ba/F3 and UT-7 cells and in OCI-AML-5 cells. The absence of SOCS6 promotes Ba/F3 and UT-7 cell proliferation induced by oncogenic internal tandem duplications of Flt3. Taken together, these results suggest that SOCS6 negatively regulates Flt3 activation, the downstream Erk signaling pathway, and cell proliferation.
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