ReviewFrontiers in endocrinology2017
The Janus Kinase (JAK) FERM and SH2 Domains: Bringing Specificity to JAK-Receptor Interactions.
Review in Frontiers in endocrinology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 125 citations in OpenAlex.
- JAK-STAT signaling pathway in cancer: from molecular mechanisms to clinical intervention.Molecular cancer · 2026Review
- JAK/STAT signaling in liver disease: a therapeutic target or a context-dependent double-edged sword?Journal of translational medicine · 2026Review
- Extracellular matrix rigidity controls breast cancer metastasis via TYK2-mediated mechanotransduction.Nature communications · 2026Article
- Identification of novelFrontiers in genetics · 2026Article
- JAK inhibition in PD-1 immunotherapy and tumor microenvironment.Frontiers in immunology · 2026Review
- Extracellular matrix rigidity controls breast cancer metastasis via TYK2-mediated mechanotransduction.bioRxiv : the preprint server for biology · 2025Article
- JAK2 46/1 (GGCC) Haplotype in Oncogenesis, as Risk Stratifier, and Indicator for Drug Resistance in Myeloproliferative Neoplasms.International journal of molecular sciences · 2025Review
- MSN/STAT3 drives cancer stemness and chemoresistance via IL-6/LPAR1 ligand receptor complex in triple-negative breast cancer.Breast cancer research : BCR · 2025Article
- Recent advances and future perspectives in small molecule JAK2 inhibitors.Future medicinal chemistry · 2025Review
- JAK-STAT Signaling in Autoimmunity and Cancer.ImmunoTargets and therapy · 2025Review
- Refining minimal engineered receptors for specific activation of on-target signaling molecules.Scientific reports · 2024Article
- Marine Bioactive Molecules as Inhibitors of the Janus Kinases: A Comparative Molecular Docking and Molecular Dynamics Simulation Approach.Current issues in molecular biology · 2024Article
- Non-Receptor Tyrosine Kinases: Their Structure and Mechanistic Role in Tumor Progression and Resistance.Cancers · 2024Review
- The Role of the JAK-STAT Pathway in Childhood B-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2024Review
- Structure of the interleukin-5 receptor complex exemplifies the organizing principle of common beta cytokine signaling.Molecular cell · 2024Article
- Omenn Syndrome in Two Infants with Different Hypomorphic Variants in Janus Kinase 3.Journal of clinical immunology · 2024Article
- Differential properties of Janus kinase inhibitors in the treatment of immune-mediated inflammatory diseases.Rheumatology (Oxford, England) · 2024Review
- Structure-function of type I and III interferons.Current opinion in immunology · 2024Review
- The oncogenic mechanisms of the Janus kinase-signal transducer and activator of transcription pathway in digestive tract tumors.Cell communication and signaling : CCS · 2024Review
- A novel approach to study multi-domain motions in JAK1's activation mechanism based on energy landscape.Briefings in bioinformatics · 2024Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Janus kinases (JAKs) are non-receptor tyrosine kinases essential for signaling in response to cytokines and interferons and thereby control many essential functions in growth, development, and immune regulation. JAKs are unique among tyrosine kinases for their constitutive yet non-covalent association with class I and II cytokine receptors, which upon cytokine binding bring together two JAKs to create an active signaling complex. JAK association with cytokine receptors is facilitated by N-terminal FERM and SH2 domains, both of which are classical mediators of peptide interactions. Together, the JAK FERM and SH2 domains mediate a bipartite interaction with two distinct receptor peptide motifs, the proline-rich "Box1" and hydrophobic "Box2," which are present in the intracellular domain of cytokine receptors. While the general sidechain chemistry of Box1 and Box2 peptides is conserved between receptors, they share very weak primary sequence homology, making it impossible to posit why certain JAKs preferentially interact with and signal through specific subsets of cytokine receptors. Here, we review the structure and function of the JAK FERM and SH2 domains in light of several recent studies that reveal their atomic structure and elucidate interaction mechanisms with both the Box1 and Box2 receptor motifs. These crystal structures demonstrate how evolution has repurposed the JAK FERM and SH2 domains into a receptor-binding module that facilitates interactions with multiple receptors possessing diverse primary sequences.
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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.