ArticleNature communications2021
Discovery of an exosite on the SOCS2-SH2 domain that enhances SH2 binding to phosphorylated ligands.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Post-translational modifications in Neuroimmune cells during neuroinflammation: integrated regulatory networks and therapeutic opportunities.Biology direct · 2026Review
- SOCS2 regulation myoblast differentiation of Hu sheep via STAT3/PSMB9 pathway.Functional & integrative genomics · 2026Article
- Insights Into Macrophage Polarization and M1/M2 Balance in Diabetic Foot Ulcers.Journal of diabetes · 2026Review
- SIRT6 Aggravates Psoriasiform Skin Inflammation Through Modulation of the SOCS2-STAT1/3 Pathway.Journal of inflammation research · 2026Article
- STAT3 SH2 Domain Aspartic Acid 661 Mutations Activate Immune Gene Programs.Journal of cellular and molecular medicine · 2026Article
- JAK-STAT Signaling in Autoimmunity and Cancer.ImmunoTargets and therapy · 2025Review
- Advancing the Understanding and Treatment of Cancer Cachexia: Mechanisms, Therapeutic Approaches, and Future Opportunities.Cancer management and research · 2025Review
- Medicinal chemistry perspective of JAK inhibitors: synthesis, biological profile, selectivity, and structure activity relationship.Molecular diversity · 2024Review
- Expression Characteristics, Immune Signature, and Prognostic Value of the SOCS Family Identified by Multiomics Integrative Analysis in Liver Cancer.Cancer reports (Hoboken, N.J.) · 2024Article
- Structure and Dynamics of Drk-SH2 Domain and Its Site-Specific Interaction with Sev Receptor Tyrosine Kinase.International journal of molecular sciences · 2024Article
- Engineered FHA domains can bind to a variety of Phosphothreonine-containing peptides.Protein engineering, design & selection : PEDS · 2024Article
- A loss of function mutation in SOCS2 results in increased inflammatory response of macrophages to TLR ligands andFrontiers in immunology · 2024Article
- Unravelling the druggability and immunological roles of the SOCS-family proteins.Frontiers in immunology · 2024Review
- Organoids transplantation attenuates intestinal ischemia/reperfusion injury in mice through L-Malic acid-mediated M2 macrophage polarization.Nature communications · 2023Article
- Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2.Nature communications · 2023Article
- Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer.Signal transduction and targeted therapy · 2023Review
- SOCS2 regulation of growth hormone signaling requires a canonical interaction with phosphotyrosine.Bioscience reports · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Suppressor of cytokine signaling (SOCS)2 protein is a key negative regulator of the growth hormone (GH) and Janus kinase (JAK)-Signal Transducers and Activators of Transcription (STAT) signaling cascade. The central SOCS2-Src homology 2 (SH2) domain is characteristic of the SOCS family proteins and is an important module that facilitates recognition of targets bearing phosphorylated tyrosine (pTyr) residues. Here we identify an exosite on the SOCS2-SH2 domain which, when bound to a non-phosphorylated peptide (F3), enhances SH2 affinity for canonical phosphorylated ligands. Solution of the SOCS2/F3 crystal structure reveals F3 as an α-helix which binds on the opposite side of the SH2 domain to the phosphopeptide binding site. F3:exosite binding appears to stabilise the SOCS2-SH2 domain, resulting in slower dissociation of phosphorylated ligands and consequently, enhances binding affinity. This biophysical enhancement of SH2:pTyr binding affinity translates to increase SOCS2 inhibition of GH signaling.
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