Affinage

TYK2

Non-receptor tyrosine-protein kinase TYK2 · UniProt P29597

Length
1187 aa
Mass
133.7 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TYK2 is a non-receptor protein tyrosine kinase that transduces cytokine receptor signaling and serves as a central regulator of type I interferon and inflammatory responses (PMID:2216457, PMID:12679810). It constitutively associates through its N-terminal domains (JH3-7) with cytokine receptor subunits including IFNAR1, and this binding both mediates signaling and is required to stabilize mature IFNAR1 at the cell surface by preventing its endosomal sequestration and degradation (PMID:9461596, PMID:12554654). Upon cytokine stimulation TYK2 becomes tyrosine-phosphorylated and acquires kinase activity, and its catalytic activity is required for full type I IFN-induced activation of STAT1-4 and for in vivo antiviral defense (PMID:8055912, PMID:22723949). TYK2 also directly phosphorylates PKR at Tyr101/Tyr293 to couple IFN signaling to translational control, and it engages diverse receptor systems including the TPO receptor, PAFR, and the urokinase pathway where it binds and activates PI3-kinase to drive cell migration (PMID:17290288, PMID:7543416, PMID:11309383, PMID:10995743). TYK2 activity is autoinhibited in cis by its pseudokinase (JH2) domain, which packs against the kinase (JH1) domain near the active site; disrupting this interface—either through engineered mutations or gain-of-function pseudokinase alleles analogous to JAK2 V617F—constitutively activates downstream STAT, MAPK, and Akt signaling (PMID:24843152, PMID:26359499, PMID:16239216). This autoinhibitory module is exploited therapeutically: the allosteric inhibitor deucravacitinib (BMS-986165) binds the JH2 domain to lock TYK2 in its inactive state with high isoform selectivity and is effective across immune cell types and inflammatory disease models (PMID:31318208, PMID:31341059). TYK2 protein levels are tuned by competing post-translational pathways—SIAH2-mediated proteasomal degradation versus AHI1-OTUD1 deubiquitinative stabilization—and the kinase is dephosphorylated by PTP1B via a defined (E/D)-pY-pY-(R/K) consensus motif (PMID:24833526, PMID:35821088, PMID:11694501). Beyond canonical immunity, TYK2 supports NK/NKT-cell tumor surveillance, brown adipose differentiation via STAT3-PRDM16, mitochondrial respiration, and survival signaling in T-ALL and ALCL lymphomas through STAT-driven BCL2/MCL1 programs (PMID:15578097, PMID:23217260, PMID:16982690, PMID:23471820, PMID:30131584). TYK2 also phosphorylates tau at Tyr29 to promote its stabilization and pathological aggregation by impairing autophagic clearance (PMID:39528671).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 1990 High

    Established the molecular identity of TYK2 as a non-receptor tyrosine kinase lacking transmembrane and SH2 domains, defining it as a cytoplasmic signaling enzyme rather than a surface receptor.

    Evidence cDNA cloning, sequencing, and chromosomal mapping

    PMID:2216457

    Open questions at the time
    • No functional partner or pathway identified at this stage
    • Domain-function relationships not yet defined
  2. 1994 High

    Linked TYK2 to type I interferon signaling by showing it is rapidly and inducibly phosphorylated and activated by IFN-alpha/beta but not IFN-gamma, placing it in a specific cytokine pathway.

    Evidence Immunoprecipitation, in vitro kinase assay, and cell fractionation after IFN stimulation

    PMID:8055912

    Open questions at the time
    • Direct substrates not identified
    • Mechanism of receptor coupling unresolved
  3. 1995 High

    Dissected TYK2 into functional modules, showing the kinase domain drives catalysis while the kinase-like (pseudokinase) region supports receptor binding and partial signaling, and broadened its receptor repertoire to the TPO receptor.

    Evidence Domain-deletion reconstitution in TYK2-deficient cells; reciprocal phosphorylation analysis in hematopoietic lines

    PMID:7531704 PMID:7543416

    Open questions at the time
    • Structural basis of pseudokinase function unknown
    • TPO receptor finding from a single lab
  4. 1997 Medium

    Defined the kinase hierarchy of IFN-alpha signaling, placing JAK1 upstream of TYK2 and showing both kinases are required for STAT activation and transcription.

    Evidence Dominant-negative kinase-deficient mutant epistasis with reporter and phosphorylation readouts

    PMID:9249040

    Open questions at the time
    • Epistasis inferred from overexpressed dominant-negatives
    • Single lab, no genetic confirmation
  5. 1998 High

    Mapped the IFNAR1-binding interface to the N-terminal JH3-7 region and showed this fragment dominantly blocks signaling, defining the receptor-association module.

    Evidence GST pulldown binding with domain fragments plus dominant-negative functional assays

    PMID:9461596

    Open questions at the time
    • Precise residue contacts not resolved
    • Whether binding stabilizes receptor not yet addressed
  6. 1998 Low

    Began defining negative regulation of TYK2 by proposing SHP-1 phosphatase association, hinting at phosphatase-mediated control.

    Evidence Co-immunoprecipitation from primary mononuclear cells

    PMID:9519782

    Open questions at the time
    • Single Co-IP without reciprocal validation or demonstrated dephosphorylation
    • Functional consequence for TYK2 activity not shown
  7. 2000 High

    Extended TYK2 signaling beyond STATs by showing it directly binds and activates PI3-kinase via p85 to drive urokinase-induced cell migration, revealing a STAT-independent output.

    Evidence Co-IP, in vitro p85 SH2 binding, PI3-K activity assay, and dominant-negative migration assay

    PMID:10995743

    Open questions at the time
    • Phosphorylation site on p85/TYK2 not mapped
    • Restricted to vascular smooth muscle context
  8. 2001 High

    Defined TYK2 regulation and localization: PTP1B dephosphorylates TYK2 via a specific consensus motif, TYK2 couples G-protein-independently to PAFR, and an NLS-like motif drives a dispensable nuclear pool.

    Evidence Substrate-trapping Co-IP with MEF KO confirmation; PAFR co-transfection with G-protein-uncoupled mutants; GFP-TYK2 imaging with membrane-targeting constructs

    PMID:11309383 PMID:11399767 PMID:11694501

    Open questions at the time
    • Functional role of nuclear TYK2 unresolved
    • PAFR coupling shown in heterologous COS-7 system
  9. 2003 High

    Revealed a kinase-independent scaffolding role: TYK2 chaperones IFNAR1 (and IL-10R2) to the plasma membrane by blocking its endocytosis and degradation, explaining loss of receptor expression in TYK2-deficient cells.

    Evidence Cell fractionation, co-localization with endosomal markers, and IFNAR1 degradation/rescue assays

    PMID:12554654

    Open questions at the time
    • Molecular mechanism of endocytosis inhibition unknown
    • Whether scaffolding requires the pseudokinase domain not tested
  10. 2003 High

    Established the in vivo physiological role of TYK2 in innate immunity, showing it drives the IFN-beta arm of LPS-induced endotoxin lethality through STAT1 and STAT4.

    Evidence Tyk2-/- mice with LPS challenge, qRT-PCR, and epistasis against IFN-beta-/- and STAT-deficient mice

    PMID:12679810 PMID:15226272

    Open questions at the time
    • Cell-type-specific contributions not fully resolved
    • Direct STAT4 activation mechanism downstream of LPS not detailed
  11. 2004 High

    Defined a tumor-surveillance function, showing TYK2 is required for NK/NKT cytotoxicity and that its loss accelerates lymphoid leukemia via impaired immune surveillance rather than cell-autonomous effects.

    Evidence Tyk2-/- mice in A-MuLV and TEL-JAK2 lymphoma models with transplantation and RAG2 double-KO experiments

    PMID:15578097

    Open questions at the time
    • Cytokine signal driving NK function not pinpointed here
    • Kinase dependence of surveillance not yet separated
  12. 2005 Medium

    Demonstrated that gain-of-function pseudokinase mutations constitutively activate TYK2 and downstream STAT/MAPK/Akt signaling, paralleling oncogenic JAK2 V617F.

    Evidence V678F mutant in Ba/F3 autonomous growth and JAK-deficient fibrosarcoma signaling assays

    PMID:16239216

    Open questions at the time
    • Structural basis of mutational activation not resolved here
    • Single lab, engineered analog mutation
  13. 2006 High

    Uncovered both kinase-dependent and kinase-independent metabolic roles, showing TYK2 maintains basal mitochondrial respiration (scaffold function) while kinase activity drives IFN-beta-induced respiration and apoptosis via STAT3.

    Evidence Tyk2-/- pro-B cells with WT and kinase-dead reconstitution, respiration/ATP assays, and CAStat3 rescue

    PMID:16982690

    Open questions at the time
    • Mechanism linking TYK2 to ETC complexes unknown
    • Restricted to pro-B cell context
  14. 2007 High

    Identified PKR as a direct TYK2 substrate, linking IFN signaling to translational control through eIF2-alpha phosphorylation.

    Evidence Co-IP, in vitro kinase assay with site-specific mutagenesis (Tyr101/Tyr293), and eIF2-alpha assays in TYK2-deficient cells

    PMID:17290288

    Open questions at the time
    • In vivo significance of PKR phosphorylation not addressed
    • Relative contribution of JAK1 vs TYK2 not quantified
  15. 2012 High

    Genetically separated catalytic from scaffold functions in vivo, showing kinase activity is required for full STAT1-4 activation, antiviral defense, and TYK2 protein stability itself.

    Evidence Tyk2(K923E) kinase-dead knockin mice with signaling, viral infection, and stability assays

    PMID:22723949

    Open questions at the time
    • Mechanism by which kinase activity stabilizes TYK2 not defined
    • Tissue-specific kinase requirements not fully mapped
  16. 2012 High

    Expanded TYK2 into metabolic development, showing it drives brown adipose differentiation via a STAT3-PRDM16 axis, with Tyk2 loss causing obesity.

    Evidence Tyk2-/- mice, CAStat3 rescue, preadipocyte differentiation, and PRDM16 Co-IP/stability assays

    PMID:23217260

    Open questions at the time
    • Upstream cytokine activating TYK2 in BAT not identified
    • Direct STAT3-PRDM16 contact not structurally resolved
  17. 2013 High

    Established TYK2 as an oncogenic dependency in T-ALL through a TYK2-STAT1-BCL2 survival pathway activated by mutations or IL-10R signaling.

    Evidence Two independent RNAi screens, knockdown in primary specimens, and STAT1/BCL2 pathway analysis

    PMID:23471820

    Open questions at the time
    • Frequency of activating mutations in patients not addressed here
    • Why STAT1 rather than other STATs drives BCL2 unclear
  18. 2014 High

    Solved the structural basis of TYK2 autoinhibition, showing the JH2 pseudokinase domain packs against JH1 near the active site to hold the kinase inactive, and that interface mutations activate it.

    Evidence 2.8 Å crystal structure of the JH2-JH1 module with interface mutagenesis and kinase assays

    PMID:24843152

    Open questions at the time
    • Conformational dynamics of activation not captured
    • Full-length/receptor-bound state not visualized
  19. 2014 High

    Characterized JH2 as an ATP-binding but catalytically dead regulatory domain whose ATP pocket can be drugged, providing the structural rationale for allosteric inhibition.

    Evidence Crystal structure of JH2 with ATP-gamma-S, ATP-pocket mutant signaling, and small-molecule co-crystal

    PMID:26359499

    Open questions at the time
    • How ATP binding to JH2 modulates JH1 in cells not fully defined
    • Inhibitor selectivity not yet demonstrated
  20. 2014 Medium

    Defined opposing degradation pathways and oncogenic fusion biology: SIAH2 drives p53-induced TYK2 proteasomal degradation, while NPM1-TYK2 fusions constitutively activate STAT signaling and drive lymphoma growth.

    Evidence SIAH2 gain/loss with proteasome inhibition and p53 activation; NPM1-TYK2 fusion characterization with kinase-dead mutant and shRNA

    PMID:24833526 PMID:25349176

    Open questions at the time
    • SIAH2 ubiquitination sites on TYK2 not mapped
    • Both findings from single labs
  21. 2015 High

    Refined the surveillance role by separating scaffold and catalytic requirements: NK maturation needs TYK2 expression while IL-12-driven IFN-gamma production strictly requires kinase activity.

    Evidence Comparison of Tyk2-/- and Tyk2(K923E) knockin NK cells in vivo and in vitro

    PMID:26451322

    Open questions at the time
    • Scaffold mechanism supporting NK maturation undefined
    • Downstream effectors of kinase-dependent IFN-gamma not detailed
  22. 2017 Medium

    Identified a non-canonical CTLA4-TYK2-STAT3 oncogenic axis in B-cell lymphoma, showing receptor ligation recruits TYK2 to drive tumor proliferation.

    Evidence CTLA4-TYK2 Co-IP, phosphorylation, and CTLA4 knockdown/antibody blockade with tumor growth assays

    PMID:28716895

    Open questions at the time
    • Direct vs indirect CTLA4-TYK2 interaction not resolved
    • Single lab
  23. 2018 Medium

    Established TYK2 as a survival dependency in ALCL through an autocrine IL-10/IL-22-TYK2-STAT1/3-MCL1 pathway, independent of ALK status.

    Evidence Tyk2-/- NPM-ALK lymphoma mouse model and human ALCL inhibitor studies with STAT/MCL1 readouts

    PMID:30131584

    Open questions at the time
    • Relative roles of IL-10 vs IL-22 not separated
    • Single lab
  24. 2019 High

    Validated JH2-targeted allosteric inhibition as a selective therapeutic strategy, showing deucravacitinib binds JH2 to block JH1 catalysis with unprecedented selectivity and recapitulates the protective TYK2 deactivating variant across immune cells and patients.

    Evidence Structure-guided medicinal chemistry, JH2 binding and kinase assays, murine disease models, and phase 1 clinical pharmacodynamics

    PMID:31318208 PMID:31341059

    Open questions at the time
    • Long-term resistance mechanisms not addressed
    • Full structural detail of inhibitor-stabilized state in cells not resolved
  25. 2020 High

    Connected TYK2 to inflammasome biology and disease-associated splicing: TYK2 kinase activity drives transcriptional induction of caspase-11 and pyroptosis, while function-altering variants modulate exon 8 inclusion required for receptor binding.

    Evidence Multiple Tyk2 genetic models (KO, K923E, myeloid-conditional) with CASP11/pyroptosis readouts; minigene splicing and eQTL analysis of disease variants

    PMID:31961910 PMID:32929218

    Open questions at the time
    • Transcription factor linking TYK2 to CASP11 not identified
    • Splicing variant effects shown largely in cell models
  26. 2022 High

    Extended TYK2 into neurodegeneration, stem cell biology, and stability control: TYK2 phosphorylates tau at Tyr29 to promote aggregation by blocking autophagy, regulates pancreatic precursor emergence and beta-cell immunogenicity, and is stabilized by an AHI1-OTUD1 deubiquitination axis.

    Evidence In vitro tau kinase assay with Tyr29 mutagenesis and P301S mouse model; TYK2-KO iPSC pancreatic differentiation; AHI1-OTUD1-TYK2 Co-IP and ubiquitination assays

    PMID:35821088 PMID:36289205 PMID:39528671

    Open questions at the time
    • Whether tau Tyr29 phosphorylation occurs in human tauopathy tissue not established
    • AHI1-OTUD1 axis from single lab
  27. 2023 High

    Revealed TYK2 as a direct target of viral immune evasion, with tick-borne flavivirus NS5 binding the TYK2 kinase domain to suppress its catalytic activity.

    Evidence Co-IP, yeast gap-repair, computational docking, in vitro TYK2 kinase assay, and mass spectrometry

    PMID:37860832

    Open questions at the time
    • Structural detail of the NS5-TYK2 complex not solved
    • In vivo contribution to viral pathogenesis not quantified
  28. 2024 High

    Demonstrated TYK2's role in autoimmune type 1 diabetes, showing IL-12-driven TYK2 signaling generates autoreactive CTLs and that selective TYK2 inhibition prevents disease onset.

    Evidence Tyk2-/- NOD mice with cross-priming and CTL cytotoxicity assays plus BMS-986165 treatment

    PMID:38351043

    Open questions at the time
    • Human translatability of T1D protection not established
    • Relative contribution of T-cell intrinsic vs DC-intrinsic TYK2 not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TYK2's distinct kinase-dependent and scaffold (receptor-stabilizing, mitochondrial, NK-maturation) functions are integrated and selectively engaged across tissues, and how this dual nature shapes therapeutic targeting, remains unresolved.
  • No unified structural model of receptor-bound, activated TYK2
  • Mechanism distinguishing scaffold from catalytic outputs per cell type unknown
  • Whether allosteric JH2 inhibitors spare scaffold functions not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016740 transferase activity 3 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005634 nucleus 1 GO:0005739 mitochondrion 1 GO:0005768 endosome 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1430728 Metabolism 2
Partners
IFNAR1OTUD1P85PKRPTP1BSIAH2STAT1STAT3

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 TYK2 is a non-receptor protein tyrosine kinase lacking a transmembrane domain and SH2 domain, encoded by a 4176-nucleotide cDNA producing a ~134 kDa protein, mapping to chromosome 19p13.2, and widely expressed in hematopoietic and non-hematopoietic cells. cDNA cloning, sequencing, hydrophobicity analysis, chromosomal mapping Oncogene High 2216457
1994 TYK2 is a 134 kDa protein that is rapidly and transiently phosphorylated on tyrosine and acquires inducible kinase activity in response to IFN-α/β but not IFN-γ; the protein localizes predominantly to the cytoplasm with a minor membrane-associated fraction, both of which are activated by IFN. Polyclonal antibody immunoprecipitation, in vitro kinase assay, cell fractionation, pervanadate treatment European journal of biochemistry High 8055912
1995 Distinct domains of TYK2 are required for different functions: the tyrosine kinase domain is required for in vitro kinase activity; a truncation retaining the kinase-like domain but lacking the tyrosine kinase domain reconstitutes IFN-α8 binding and partial signaling; deletion of both kinase domains abolishes all detectable activity; demonstrating sequential domain-function relationships. Stable transfection of domain-deletion mutants in TYK2-deficient cells, in vitro kinase assay, ligand-binding assay, signaling assays The Journal of biological chemistry High 7531704
1995 Activation of the TPO receptor (c-MPL) rapidly induces tyrosine phosphorylation of both JAK2 and TYK2 (but not JAK1 or JAK3) in hematopoietic cell lines, followed by phosphorylation of STAT1, STAT3, and STAT5 and formation of specific DNA-binding complexes. Immunoprecipitation, Western blot, gel-shift assay in factor-dependent hematopoietic cell lines Experimental hematology Medium 7543416
1997 Kinase-deficient (dominant-negative) forms of both TYK2 and JAK1 independently suppress IFN-α-induced STAT phosphorylation and transcriptional activation; differential effects on kinase auto-phosphorylation suggest JAK1 functions upstream of TYK2 in the IFN-α signaling cascade. Transient transfection of kinase-deficient mutants, reporter gene assay, immunoprecipitation/Western blot for STAT phosphorylation European journal of biochemistry Medium 9249040
1998 The IFNaR1-binding domain of TYK2 maps to the amino-terminal ~600 amino acids (JH3-7), with JH6 and JH3 domains as major interaction sites; this N-terminal fragment acts dominantly to inhibit IFN-α-dependent transcription and phosphorylation of TYK2, STAT1, and STAT2. In vitro GST pulldown binding assays, dominant-negative transfection, reporter gene assay, phosphorylation analysis The Journal of biological chemistry High 9461596
1998 SHP-1 associates with TYK2 (but not other JAK family members) in normal cells, and this interaction is reduced in a patient with familial hemophagocytic lymphohistiocytosis, suggesting TYK2 is regulated by SHP-1. Co-immunoprecipitation from peripheral blood mononuclear cells Leukemia Low 9519782
1999 The growth hormone receptor (GHR) associates with TYK2 (as well as JAK1 and JAK2) in human liver tissue, as detected by immunoprecipitation. Immunoprecipitation from human liver tissue followed by immunoblotting Growth hormone & IGF research Low 10502458
2000 TYK2 interacts with and activates PI3-kinase in response to urokinase (uPA) in vascular smooth muscle cells: the PI3-K regulatory subunit p85 co-immunoprecipitates specifically with TYK2 (not JAK1/2/3), TYK2 directly binds either SH2 domain of p85 in a uPA-dependent manner, and dominant-negative TYK2 abolishes PI3-K activation and uPA-induced cell migration. Co-immunoprecipitation, in vitro binding assay, dominant-negative transfection, PI3-K activity assay, migration assay The Journal of biological chemistry High 10995743
2001 JAK2 and TYK2 are substrates of PTP1B: PTP1B recognizes the consensus motif (E/D)-pY-pY-(R/K) present in both kinases (analogous to the insulin receptor dephosphorylation site); a substrate-trapping PTP1B mutant stably interacts with JAK2 and TYK2 after IFN stimulation; wild-type PTP1B expression inhibits IFN-dependent transcriptional activation; JAK1, which lacks this consensus site, is not a PTP1B substrate. Substrate-trapping mutant co-immunoprecipitation, PTP1B overexpression/reporter assay, PTP1B-deficient MEF phosphorylation analysis The Journal of biological chemistry High 11694501
2001 TYK2 co-immunoprecipitates and co-localizes with the platelet-activating factor receptor (PAFR) independently of ligand binding, mediated by the N-terminus of TYK2; PAF stimulation induces TYK2 phosphorylation and subsequent STAT1/2/3/5 activation; PAFR mutants unable to couple to G-proteins still activate TYK2, indicating G-protein-independent TYK2 activation. Co-immunoprecipitation, deletion mutant mapping, Tyk2/PAFR co-transfection in COS-7, STAT phosphorylation/nuclear translocation assay, G-protein-uncoupled PAFR mutant analysis The Journal of biological chemistry Medium 11309383
2001 TYK2 contains a nuclear localization signal (NLS)-like arginine-rich motif within its receptor-interaction region that is required for nuclear localization; GFP-TYK2 distributes throughout the cell including the nucleus; a membrane-targeted TYK2 still supports IFN-α transcriptional and antiviral responses, showing the nuclear TYK2 pool is dispensable for these responses. GFP fusion direct fluorescence, immunostaining, membrane-targeting construct functional assays The Journal of biological chemistry Medium 11399767
2003 TYK2 is essential for stable cell-surface expression of the IFNAR1 receptor subunit: in the absence of TYK2, mature IFNAR1 accumulates in a perinuclear endosomal compartment overlapping with recycling transferrin receptors and EEA1-positive vesicles rather than the plasma membrane; TYK2 co-expression greatly enhances surface IFNAR1 by slowing its degradation through inhibition of endocytosis; TYK2 also promotes plasma membrane localization of the IL-10 receptor R2 subunit. Cell fractionation, immunostaining, co-localization with endosomal markers (transferrin receptor, EEA1), co-expression experiments, IFNAR1 degradation assay The EMBO journal High 12554654
2003 Tyk2-null mice are resistant to high-dose LPS-induced endotoxin shock; Tyk2-null macrophages show reduced basal and LPS-induced IFN-β and IFN-α4 mRNA expression; systemic NO and proinflammatory cytokine production and TNF responses are normal, placing TYK2 specifically in the IFN-β-dependent arm of LPS lethality. Tyk2-/- mice, LPS challenge survival, qRT-PCR, cytokine measurement, IFN-β-/- and STAT1-/- comparison Nature immunology High 12679810
2004 Tyk2 deficiency reduces LPS-induced IFN-β and IFN-γ production in macrophages in vivo; Tyk2-/- mice are resistant to LPS shock; Tyk2 is required for both STAT1 (IFN-β arm) and STAT4 (IFN-γ/NK cell arm) activation in response to LPS, placing TYK2 upstream of both STAT1 and STAT4 in endotoxin signaling. Tyk2-/-, STAT1-/-, STAT4-/- mice, LPS challenge, cytokine ELISA, signaling analysis International immunology High 15226272
2004 TYK2 is required for NK and NKT cell cytotoxic activity against tumor-derived cells; TYK2-/- mice show increased incidence and shortened latency of Abelson-induced B lymphoid leukemia/lymphoma and TEL-JAK2-induced T lymphoid leukemia due to impaired tumor surveillance, not cell-autonomous effects of transformed cells. Tyk2-/- mice, A-MuLV and TEL-JAK2 lymphoma models, NK/NKT cytotoxicity assay, transplantation experiments, RAG2/TYK2 double-KO The Journal of clinical investigation High 15578097
2005 The homologous V617F pseudokinase domain mutation in TYK2 (V678F) leads to constitutive TYK2 activation, autonomous growth of cytokine-dependent cells, and constitutive STAT5, STAT3, MAPK, and Akt signaling, establishing that gain-of-function pseudokinase mutations activate TYK2 by a mechanism analogous to the JAK2 V617F mutation in polycythemia vera. Ba/F3 cell autonomous growth assay, signaling analysis in JAK-deficient fibrosarcoma cells, constitutive phosphorylation Western blot The Journal of biological chemistry Medium 16239216
2006 TYK2 expression is required for maintenance of mitochondrial respiration (complexes I, III, IV) and steady-state ATP levels in pro-B cells; reconstitution with either wild-type or kinase-inactive TYK2 restores basal mitochondrial respiration, but kinase activity is required for IFN-β-induced complex I-dependent respiration and apoptosis; constitutively active STAT3 rescues mitochondrial respiration in TYK2-null cells treated with IFN-β. Tyk2-/- pro-B cells, oxygen consumption assay, ATP measurement, electron transport chain complex activity assays, kinase-inactive mutant reconstitution, CAStat3 rescue Molecular and cellular biology High 16982690
2007 PKR physically interacts with TYK2 (and JAK1) in unstimulated cells; these interactions increase after IFN treatment; activated TYK2 and JAK1 phosphorylate PKR at Tyr101 and Tyr293 in vitro and in vivo; TYK2-deficient cells show impaired IFN-induced eIF2α phosphorylation and protein synthesis inhibition, establishing TYK2 as a direct upstream kinase of PKR linking IFN signaling to translational control. Co-immunoprecipitation, in vitro kinase assay with site-specific mutagenesis, eIF2α phosphorylation assay in TYK2-deficient cells EMBO reports High 17290288
2012 TYK2 kinase activity (not just TYK2 expression) is required for full type I IFN-induced activation of STAT1-4 and in vivo antiviral defense; kinase-inactive TYK2 (K923E) mice are viable but show impaired IFN signaling; TYK2 kinase activity is also required for TYK2 protein stability; an inhibitory function of kinase-inactive TYK2 was observed only upon overexpression in vitro, not in vivo. Gene-targeted Tyk2(K923E) knockin mice, STAT1-4 phosphorylation, viral infection model, protein stability assay PloS one High 22723949
2012 Tyk2 and Stat3 regulate brown adipose tissue (BAT) differentiation from Myf5+ progenitors: Tyk2-/- mice develop progressive obesity due to defective BAT; expression of TYK2 or constitutively active STAT3 restores differentiation in Tyk2-/- brown preadipocytes; Stat3 binds to PRDM16 (a master BAT regulator) and enhances PRDM16 protein stability. Tyk2-/- mice, CAStat3 transgene rescue, preadipocyte differentiation assay, PRDM16 co-immunoprecipitation/stability assay Cell metabolism High 23217260
2013 TYK2 promotes T-ALL cell survival through a TYK2→STAT1→BCL2 pathway: TYK2 is activated by gain-of-function TYK2 mutations or IL-10 receptor signaling in T-ALL; TYK2 knockdown consistently induces cell death in primary T-ALL specimens and cell lines; BCL2 is upregulated downstream of STAT1 in this pathway. RNAi screens (two independent), TYK2 knockdown in primary specimens and cell lines, small-molecule JAK inhibitor, STAT1/BCL2 pathway analysis Cancer discovery High 23471820
2014 The TYK2 pseudokinase (JH2) domain interacts with the kinase (JH1) domain near the kinase active site and holds the kinase inactive (autoinhibition); mutations at the pseudokinase-kinase interface analogous to cancer-associated JAK2 alleles (V617F, exon 12) increase TYK2 kinase activity in vitro, demonstrating JAK pseudokinases are autoinhibitory domains. 2.8 Å crystal structure of TYK2 pseudokinase-kinase module, in vitro kinase assay with interface mutations PNAS High 24843152
2014 NPM1-TYK2 fusion protein (generated by chromosomal translocation) drives constitutive TYK2, STAT1, STAT3, and STAT5 activation; a kinase-defective NPM1-TYK2 mutant abrogates STAT1/3/5 signaling; TYK2 shRNA silencing abolishes lymphoma cell growth in cutaneous CD30+ lymphoproliferative disorders. Whole-transcriptome sequencing, FISH, constitutive signaling analysis, kinase-dead mutant, shRNA knockdown Blood Medium 25349176
2014 SIAH2 (E3 ubiquitin ligase) promotes proteasomal degradation of TYK2, thereby suppressing TYK2-STAT3 signaling in lung cancer cells; p53 activation induces SIAH2, depletes TYK2, and abrogates STAT1 and STAT3 tyrosine phosphorylation. SIAH2 overexpression/knockdown, TYK2 protein level analysis, proteasome inhibitor experiment, p53 activation assay, STAT phosphorylation Oncotarget Medium 24833526
2015 Crystal structure of TYK2 JH2 (pseudokinase) in complex with ATP-γS shows ATP binding stabilizes the protein without major conformational changes; TYK2 JH2 lacks phosphotransfer activity; mutation of the JH2 ATP-binding pocket increases basal TYK2 phosphorylation and downstream signaling; structural differences around helix αAL provide the basis for differential catalytic activities among JAK family JH2 domains; co-crystal with a small molecule inhibitor demonstrates JH2 druggability. Crystal structure determination, ATP-γS binding biochemistry/biophysics, JH2 ATP-pocket mutant signaling analysis, small-molecule co-crystal The Journal of biological chemistry High 26359499
2015 In vivo NK cell-mediated tumor surveillance requires TYK2 expression but only partially requires TYK2 kinase activity: Tyk2-/- NK cells have severely impaired cytotoxicity and maturation; Tyk2(K923E) kinase-inactive NK cells show less maturation defect but reduced IFN-γ production in response to IL-12 or activating receptor stimulation is strictly kinase-dependent. Tyk2-/- and Tyk2(K923E) knockin mice, in vivo tumor growth assay, NK cell cytotoxicity assay, IFN-γ production, NK cell maturation analysis Oncoimmunology High 26451322
2017 CTLA4-CD86 ligation recruits and activates TYK2, which then activates STAT3 in B-cell lymphomas; silencing or antibody blockade of CTLA4 in B-cell lymphoma cells reduces TYK2/STAT3 activity, tumor cell proliferation, and induces apoptosis, establishing a CTLA4→TYK2→STAT3 oncogenic signaling axis independent of T-cell inhibition. Co-immunoprecipitation (CTLA4-TYK2), TYK2/STAT3 phosphorylation, CTLA4 knockdown/antibody blockade, tumor growth assay Cancer research Medium 28716895
2018 TYK2 drives ALCL cell survival through an autocrine IL-10/IL-22→TYK2→STAT1/STAT3→MCL1 pathway; genetic disruption of Tyk2 in an NPM-ALK mouse lymphoma model delays tumor onset and prolongs survival with reduced STAT1, STAT3 phosphorylation and MCL1 expression; TYK2 inhibitors induce apoptosis in ALCL cells regardless of ALK-fusion status. Tyk2-/- mouse lymphoma model, human ALCL cell line TYK2 inhibition, STAT1/3 phosphorylation, MCL1 expression analysis Leukemia Medium 30131584
2019 BMS-986165 (deucravacitinib) binds to the TYK2 pseudokinase (JH2) domain with high affinity and allosterically inhibits TYK2 JH1 catalytic activity; structure-guided design exploiting water displacement at the JH2 domain led to unprecedented JAK isoform and kinome selectivity; the compound is efficacious in murine lupus nephritis and IBD models. Structure-guided medicinal chemistry, JH2 domain binding assay, TYK2 kinase activity assay, murine disease models Journal of medicinal chemistry High 31318208
2019 BMS-986165 allosterically blocks receptor-stimulated TYK2 activation by stabilizing the JH2 regulatory domain, recapitulating the phenotype of the naturally protective deactivating TYK2 coding variant; this blocks signaling and function in human TH17, TH1, B cells, and myeloid cells both in vitro and in a phase 1 clinical trial. Biochemical TYK2 activity assay, cellular signaling assays (multiple immune cell types), clinical pharmacodynamic studies Science translational medicine High 31341059
2019 TYK2 regulates IκB-ζ expression in IL-17-stimulated keratinocytes: TYK2 catalytic activity and its substrate STAT3 are required for IκB-ζ promoter activity (transcriptional activation); separately, IL-17-ACT1 signaling stabilizes IκB-ζ mRNA post-transcriptionally; these two pathways act independently but complementarily. Tyk2-/- mouse skin inflammation model, IκB-ζ promoter-luciferase assay, TYK2 catalytic inhibitor, STAT3 analysis, mRNA stability assay ImmunoHorizons Medium 31356171
2020 TYK2 is a critical upstream regulator of the non-canonical inflammasome component caspase-11 (CASP11): absence of TYK2 or its kinase activity impairs transcriptional induction of CASP11, protects mice from LPS-induced lethality, and inhibits macrophage pyroptosis and mature IL-1β/IL-18 release in response to intracellular LPS; myeloid-cell-specific TYK2 deletion recapitulates these effects in vivo. Tyk2-/-, kinase-inactive Tyk2(K923E), and myeloid-conditional Tyk2 KO mice; CASP11 expression, pyroptosis, IL-1β/IL-18 assay, pharmacological TYK2 inhibition in BMDMs Cell death and differentiation High 32929218
2020 Two disease-associated TYK2 variants (rs12720270 and rs2304256/Val362Phe) promote exon 8 inclusion; exon 8 is essential for TYK2 binding to cognate receptors; rs2304256 also mildly enhances TYK2 expression in whole blood, suggesting these variants increase TYK2 function through altered splicing. Transcript analysis in genotyped EBV-B cells, CRISPR/Cas9-edited cells, minigene splicing assay, eQTL analysis in primary monocytes and whole blood PloS one Medium 31961910
2022 TYK2 phosphorylates tau at tyrosine 29 (Tyr29), leading to tau stabilization and promotion of tau aggregation in human cells; TYK2-mediated Tyr29 phosphorylation interferes with autophagic clearance of tau; TYK2-mediated phosphorylation facilitates pathological tau accumulation in P301S tau-transgenic mice; Tyk2 knockdown reduces total and pathogenic tau levels and rescues gliosis in a tauopathy mouse model. In vitro phosphorylation assay, site-specific mutagenesis (Tyr29), autophagic clearance assay, P301S tau-transgenic mouse model with Tyk2 knockdown, tau aggregation assay Nature neuroscience High 39528671
2022 AHI1 recruits the deubiquitinase OTUD1 to deubiquitinate and stabilize TYK2, thereby maintaining basal type I IFN signaling activity in macrophages; depression-associated reduction in AHI1 levels downregulates TYK2 protein and IFN-I signaling. Co-immunoprecipitation (AHI1-OTUD1-TYK2), ubiquitination assay, TYK2 protein stability analysis, AHI1 knockdown in macrophages from MDD patients and mouse models Cell research Medium 35821088
2022 JAK2/TYK2 are recruited onto MyD88 downstream of the CD91-TLR4 complex upon extracellular HSP90α stimulation and induce STAT3 phosphorylation/activation, contributing to macrophage M2-polarization and regulation of M1/M2-related gene expression. Co-immunoprecipitation (MyD88-JAK2/TYK2), STAT3 phosphorylation assay, gene expression analysis in macrophages Cells Low 35053345
2022 Loss of TYK2 in human iPSC-derived pancreatic endocrine precursors compromises their emergence by regulating KRAS expression; loss or inhibition of TYK2 in stem cell-islets prevents IFNα-induced MHC Class I and Class II upregulation, reducing CD8+ T-cell cytotoxicity against β-cells. TYK2 knockout human iPSCs directed into pancreatic endocrine lineage, KRAS expression analysis, MHC-I/II flow cytometry, CD8+ T-cell cytotoxicity assay, TYK2 inhibitor treatment Nature communications Medium 36289205
2023 The NS5 protein of tick-borne flaviviruses (TBEV and LIV) antagonizes JAK-STAT signaling by directly interacting with the TYK2 kinase domain and reducing its catalytic activity; a 10-residue stretch in the NS5 RNA-dependent RNA polymerase domain is critical for this interaction, which is conserved across mammalian TYK2 orthologs but absent in mosquito-borne NS5. Co-immunoprecipitation, yeast gap-repair assay, computational protein-protein docking, in vitro TYK2 kinase assay, mass spectrometry EMBO reports High 37860832
2024 TYK2 signaling (via IL-12 in CD8+ T cells) is required for development of autoreactive T-BET+ cytotoxic T lymphocytes and for CD8+ dendritic cell-driven cross-priming in the pancreatic lymph node; Tyk2-deficient CTLs display reduced cytotoxicity; TYK2 inhibition (BMS-986165) suppresses CTL expansion and β-cell inflammation and prevents autoimmune T1D onset in NOD mice. Tyk2-/- NOD mice, IL-12 signaling analysis in CD8+ T cells, cross-priming assay, CTL cytotoxicity assay, BMS-986165 treatment of NOD mice Nature communications High 38351043

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B. The Journal of biological chemistry 381 11694501
1990 tyk2, prototype of a novel class of non-receptor tyrosine kinase genes. Oncogene 313 2216457
2015 Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome. The Journal of experimental medicine 286 26304966
2019 Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165. Journal of medicinal chemistry 280 31318208
2003 Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock. Nature immunology 280 12679810
2019 Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain. Science translational medicine 228 31341059
2022 Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial. Journal of the American Academy of Dermatology 222 36115523
2016 Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity. Science translational medicine 213 27807284
2014 Structure of the pseudokinase-kinase domains from protein kinase TYK2 reveals a mechanism for Janus kinase (JAK) autoinhibition. Proceedings of the National Academy of Sciences of the United States of America 186 24843152
2003 The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression. The EMBO journal 181 12554654
2022 Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis. Annals of the rheumatic diseases 166 35241426
1995 The thrombopoietin receptor c-MPL activates JAK2 and TYK2 tyrosine kinases. Experimental hematology 164 7543416
2005 JAK1 and Tyk2 activation by the homologous polycythemia vera JAK2 V617F mutation: cross-talk with IGF1 receptor. The Journal of biological chemistry 145 16239216
1995 Distinct domains of the protein tyrosine kinase tyk2 required for binding of interferon-alpha/beta and for signal transduction. The Journal of biological chemistry 134 7531704
2020 JAK Inhibitors for Treatment of Psoriasis: Focus on Selective TYK2 Inhibitors. Drugs 129 32020553
2015 TYK2 protein-coding variants protect against rheumatoid arthritis and autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune complex traits. PloS one 124 25849893
2013 TYK2-STAT1-BCL2 pathway dependence in T-cell acute lymphoblastic leukemia. Cancer discovery 120 23471820
2015 TYK2, a Candidate Gene for Type 1 Diabetes, Modulates Apoptosis and the Innate Immune Response in Human Pancreatic β-Cells. Diabetes 107 26239055
2011 Tyrosine kinase 2 (TYK2) in cytokine signalling and host immunity. Frontiers in bioscience (Landmark edition) 91 21622231
2015 Structural and Functional Characterization of the JH2 Pseudokinase Domain of JAK Family Tyrosine Kinase 2 (TYK2). The Journal of biological chemistry 88 26359499
2014 Inhibition of TYK2 and JAK1 ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting IL-22 and the IL-23/IL-17 axis. Journal of immunology (Baltimore, Md. : 1950) 88 25156366
2013 Lead identification of novel and selective TYK2 inhibitors. European journal of medicinal chemistry 86 23867602
2014 A novel recurrent NPM1-TYK2 gene fusion in cutaneous CD30-positive lymphoproliferative disorders. Blood 83 25349176
2012 Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity. Cell metabolism 74 23217260
2004 The role of Tyk2, Stat1 and Stat4 in LPS-induced endotoxin signals. International immunology 73 15226272
2000 Urokinase stimulates human vascular smooth muscle cell migration via a phosphatidylinositol 3-kinase-Tyk2 interaction. The Journal of biological chemistry 71 10995743
2023 Deucravacitinib is an allosteric TYK2 protein kinase inhibitor FDA-approved for the treatment of psoriasis. Pharmacological research 63 36754102
2023 Mendelian randomization and clinical trial evidence supports TYK2 inhibition as a therapeutic target for autoimmune diseases. EBioMedicine 62 36842216
2023 Tyk2 Targeting in Immune-Mediated Inflammatory Diseases. International journal of molecular sciences 60 36834806
2019 Selective Tyk2 inhibitors as potential therapeutic agents: a patent review (2015-2018). Expert opinion on therapeutic patents 59 30621465
2013 Tyk2 is a therapeutic target for psoriasis-like skin inflammation. International immunology 59 24345760
2012 TYK2 kinase activity is required for functional type I interferon responses in vivo. PloS one 59 22723949
2020 TYK2 inhibition reduces type 3 immunity and modifies disease progression in murine spondyloarthritis. The Journal of clinical investigation 58 32149730
1994 Activation of the protein tyrosine kinase tyk2 by interferon alpha/beta. European journal of biochemistry 58 8055912
2004 TYK2 is a key regulator of the surveillance of B lymphoid tumors. The Journal of clinical investigation 56 15578097
2010 Meta-analysis of TYK2 gene polymorphisms association with susceptibility to autoimmune and inflammatory diseases. Molecular biology reports 55 21140222
2023 Allosteric TYK2 inhibition: redefining autoimmune disease therapy beyond JAK1-3 inhibitors. EBioMedicine 54 37863021
2022 Impaired IL-23-dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency. The Journal of experimental medicine 54 36094518
2020 Discovery of Tyrosine Kinase 2 (TYK2) Inhibitor (PF-06826647) for the Treatment of Autoimmune Diseases. Journal of medicinal chemistry 54 32787094
2007 Association of polymorphisms across the tyrosine kinase gene, TYK2 in UK SLE families. Rheumatology (Oxford, England) 54 17384181
2019 TYK2: An Upstream Kinase of STATs in Cancer. Cancers 53 31694222
2003 Enhanced Th2 cell-mediated allergic inflammation in Tyk2-deficient mice. Journal of immunology (Baltimore, Md. : 1950) 53 12517976
2001 G-protein-independent activation of Tyk2 by the platelet-activating factor receptor. The Journal of biological chemistry 50 11309383
2022 Extracellular HSP90α Induces MyD88-IRAK Complex-Associated IKKα/β-NF-κB/IRF3 and JAK2/TYK2-STAT-3 Signaling in Macrophages for Tumor-Promoting M2-Polarization. Cells 48 35053345
2022 The type 1 diabetes gene TYK2 regulates β-cell development and its responses to interferon-α. Nature communications 48 36289205
2020 Molecular and Cellular Responses to the TYK2/JAK1 Inhibitor PF-06700841 Reveal Reduction of Skin Inflammation in Plaque Psoriasis. The Journal of investigative dermatology 47 31972249
2017 CTLA4 Promotes Tyk2-STAT3-Dependent B-cell Oncogenicity. Cancer research 46 28716895
2021 TYK2 as a therapeutic target in the treatment of autoimmune and inflammatory diseases. Immunotherapy 45 34235974
2015 Influence of TYK2 in systemic sclerosis susceptibility: a new locus in the IL-12 pathway. Annals of the rheumatic diseases 45 26338038
2022 Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis. Cell research 43 35821088
2018 Dependency on the TYK2/STAT1/MCL1 axis in anaplastic large cell lymphoma. Leukemia 40 30131584
2007 Interferons induce tyrosine phosphorylation of the eIF2alpha kinase PKR through activation of Jak1 and Tyk2. EMBO reports 40 17290288
2024 TYK2: an emerging therapeutic target in rheumatic disease. Nature reviews. Rheumatology 38 38467779
1998 Definition of the interferon-alpha receptor-binding domain on the TYK2 kinase. The Journal of biological chemistry 37 9461596
2007 Tyk2 expression and its signaling enhances the invasiveness of prostate cancer cells. Biochemical and biophysical research communications 36 17920038
2018 Compound heterozygous TYK2 mutations underlie primary immunodeficiency with T-cell lymphopenia. Scientific reports 34 29725107
2023 Deucravacitinib: The First FDA-Approved Oral TYK2 Inhibitor for Moderate to Severe Plaque Psoriasis. The Annals of pharmacotherapy 33 37341177
2015 TYK2 Promoter Variant and Diabetes Mellitus in the Japanese. EBioMedicine 33 26288847
2006 Tyk2 tyrosine kinase expression is required for the maintenance of mitochondrial respiration in primary pro-B lymphocytes. Molecular and cellular biology 33 16982690
2022 Clinical Implications of Targeting the JAK-STAT Pathway in Psoriatic Disease: Emphasis on the TYK2 Pathway. Journal of cutaneous medicine and surgery 32 36519621
2020 Two common disease-associated TYK2 variants impact exon splicing and TYK2 dosage. PloS one 32 31961910
2015 In vivo tumor surveillance by NK cells requires TYK2 but not TYK2 kinase activity. Oncoimmunology 31 26451322
2014 SIAH2 antagonizes TYK2-STAT3 signaling in lung carcinoma cells. Oncotarget 31 24833526
2012 Selective JAK1 inhibitor and selective Tyk2 inhibitor patents. Expert opinion on therapeutic patents 31 22971156
1997 Kinase-deficient forms of Jak1 and Tyk2 inhibit interferon alpha signaling in a dominant manner. European journal of biochemistry 31 9249040
2023 Efficacy and safety of the selective TYK2 inhibitor, deucravacitinib, in Japanese patients with moderate to severe plaque psoriasis: Subgroup analysis of a randomized, double-blind, placebo-controlled, global phase 3 trial. The Journal of dermatology 28 36882942
2001 The receptor interaction region of Tyk2 contains a motif required for its nuclear localization. The Journal of biological chemistry 28 11399767
2022 TYK2 in Immune Responses and Treatment of Psoriasis. Journal of inflammation research 27 36147687
2004 Control of Leishmania major in the absence of Tyk2 kinase. European journal of immunology 27 14768057
2021 TYK2 inhibition and its potential in the treatment of chronic inflammatory immune diseases. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG 26 34580985
2016 Clinical genomic profiling identifies TYK2 mutation and overexpression in patients with neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors. Cancer 26 27875628
2022 Novel Small Molecule Tyrosine Kinase 2 Pseudokinase Ligands Block Cytokine-Induced TYK2-Mediated Signaling Pathways. Frontiers in immunology 25 35693820
2020 TYK2 licenses non-canonical inflammasome activation during endotoxemia. Cell death and differentiation 25 32929218
2023 Deucravacitinib: a novel TYK2 inhibitor for the treatment of moderate-to-severe psoriasis. Journal of psoriasis and psoriatic arthritis 23 38188537
2020 TYK2 in Tumor Immunosurveillance. Cancers 23 31936322
2022 Selective TYK2 inhibitors as potential therapeutic agents: a patent review (2019-2021). Expert opinion on therapeutic patents 22 35001782
2021 TYK2 in Cancer Metastases: Genomic and Proteomic Discovery. Cancers 22 34439323
2012 Associations between PXK and TYK2 polymorphisms and systemic lupus erythematosus: a meta-analysis. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 21 22592861
2024 TYK2 signaling promotes the development of autoreactive CD8+ cytotoxic T lymphocytes and type 1 diabetes. Nature communications 20 38351043
2024 TYK2 regulates tau levels, phosphorylation and aggregation in a tauopathy mouse model. Nature neuroscience 20 39528671
2023 MEK Inhibition Synergizes with TYK2 Inhibitors in NF1-Associated Malignant Peripheral Nerve Sheath Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 20 36799629
2021 Therapeutic Advantage of Tyk2 Inhibition for Treating Autoimmune and Chronic Inflammatory Diseases. Biological & pharmaceutical bulletin 20 34719635
2019 IκB-ζ Expression Requires Both TYK2/STAT3 Activity and IL-17-Regulated mRNA Stabilization. ImmunoHorizons 20 31356171
2014 Conditional ablation of TYK2 in immunity to viral infection and tumor surveillance. Transgenic research 19 24696087
2019 NK Cells Require Cell-Extrinsic and -Intrinsic TYK2 for Full Functionality in Tumor Surveillance and Antibacterial Immunity. Journal of immunology (Baltimore, Md. : 1950) 18 30718299
2023 Tick-borne flavivirus NS5 antagonizes interferon signaling by inhibiting the catalytic activity of TYK2. EMBO reports 17 37860832
2020 A TYK2 Gene Mutation c.2395G>A Leads to TYK2 Deficiency: A Case Report and Literature Review. Frontiers in pediatrics 17 32537443
2019 TYK2 promotes malignant peripheral nerve sheath tumor progression through inhibition of cell death. Cancer medicine 17 31278855
2018 Comprehensive assessment of the association between genes on JAK-STAT pathway (IFIH1, TYK2, IL-10) and systemic lupus erythematosus: a meta-analysis. Archives of dermatological research 17 30171347
1998 Reduced Tyk2/SHP-1 interaction and lack of SHP-1 mutation in a kindred of familial hemophagocytic lymphohistiocytosis. Leukemia 17 9519782
2019 Catalytically Impaired TYK2 Variants are Protective Against Childhood- and Adult-Onset Systemic Lupus Erythematosus in Mexicans. Scientific reports 16 31434951
2012 Type I IFN receptor controls activated TYK2 in the nucleus: implications for EAE therapy. Journal of neuroimmunology 16 23110939
2011 The role of Tyk2 in regulation of breast cancer growth. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 16 21864028
2021 Novel mutations of TYK2 leading to divergent clinical phenotypes. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 15 34569645
2012 Docking protein Gab2 regulates mucin expression and goblet cell hyperplasia through TYK2/STAT6 pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 15 22859374
2023 A novel highly selective allosteric inhibitor of tyrosine kinase 2 (TYK2) can block inflammation- and autoimmune-related pathways. Cell communication and signaling : CCS 14 37845748
2023 Therapeutic potential of a synthetic dual JAK1/TYK2 inhibitor in inflammatory bowel disease. International immunopharmacology 14 37988912
2022 Discovery of a potent and subtype-selective TYK2 degrader based on an allosteric TYK2 inhibitor. Bioorganic & medicinal chemistry letters 14 36414177
1999 The growth hormone receptor associates with Jak1, Jak2 and Tyk2 in human liver. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 14 10502458
2024 Safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral allosteric TYK2 inhibitor ESK-001 using a randomized, double-blind, placebo-controlled study design. Clinical and translational science 13 39604226

Missed literature

Know a paper Affinage missed for TYK2? Flag it for the maintainers and the community.

No submissions yet.