ArticleThe Journal of biological chemistry2011
Structural basis for c-KIT inhibition by the suppressor of cytokine signaling 6 (SOCS6) ubiquitin ligase.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 79 citations in OpenAlex.
- Article
- The Neglected Suppressor of Cytokine Signalling (SOCS): SOCS4-7.Inflammation · 2025Review
- Genome-wide association study of chlamydia reinfection in African American women.Frontiers in immunology · 2025Article
- Unravelling the druggability and immunological roles of the SOCS-family proteins.Frontiers in immunology · 2024Review
- SOCS1 is a critical checkpoint in immune homeostasis, inflammation and tumor immunity.Frontiers in immunology · 2024Review
- Article
- Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2.Nature communications · 2023Article
- Article
- Role and significance of c-KIT receptor tyrosine kinase in cancer: A review.Bosnian journal of basic medical sciences · 2022Review
- The Emerging Role of Suppressors of Cytokine Signaling (SOCS) in the Development and Progression of Leukemia.Cancers · 2021Review
- Article
- E3 Ligase Ligands for PROTACs: How They Were Found and How to Discover New Ones.SLAS discovery : advancing life sciences R & D · 2021Review
- SOCS6 promotes radiosensitivity and decreases cancer cell stemness in esophageal squamous cell carcinoma by regulating c-Kit ubiquitylation.Cancer cell international · 2021Article
- The GTPase-activating protein p120RasGAP has an evolutionarily conserved "FLVR-unique" SH2 domain.The Journal of biological chemistry · 2020Article
- Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFβ Pathway.International journal of molecular sciences · 2020Article
- Structural insights into substrate recognition by the SOCS2 E3 ubiquitin ligase.Nature communications · 2019Article
- miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate cell proliferation and apoptosis in NSCLC.Cell death & disease · 2019Article
- Engineered SH2 domains with tailored specificities and enhanced affinities for phosphoproteome analysis.Protein science : a publication of the Protein Society · 2019Article
- Surface Loops in a Single SH2 Domain Are Capable of Encoding the Spectrum of Specificity of the SH2 Family.Molecular & cellular proteomics : MCP · 2019Article
- Negative regulators of STAT3 signaling pathway in cancers.Cancer management and research · 2019Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 7 countries.
Funding
Abstract
The c-KIT receptor tyrosine kinase mediates the cellular response to stem cell factor (SCF). Whereas c-KIT activity is important for the proliferation of hematopoietic cells, melanocytes and germ cells, uncontrolled c-KIT activity contributes to the growth of diverse human tumors. Suppressor of cytokine signaling 6 (SOCS6) is a member of the SOCS family of E3 ubiquitin ligases that can interact with c-KIT and suppress c-KIT-dependent pathways. Here, we analyzed the molecular mechanisms that determine SOCS6 substrate recognition. Our results show that the SH2 domain of SOCS6 is essential for its interaction with c-KIT pY568. The 1.45-Å crystal structure of SOCS6 SH2 domain bound to the c-KIT substrate peptide (c-KIT residues 564-574) revealed a highly complementary and specific interface giving rise to a high affinity interaction (K(d) = 0.3 μm). Interestingly, the SH2 binding pocket extends to substrate residue position pY+6 and envelopes the c-KIT phosphopeptide with a large BG loop insertion that contributes significantly to substrate interaction. We demonstrate that SOCS6 has ubiquitin ligase activity toward c-KIT and regulates c-KIT protein turnover in cells. Our data support a role of SOCS6 as a feedback inhibitor of SCF-dependent signaling and provides molecular data to account for target specificity within the SOCS family of ubiquitin ligases.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.