Affinage

JAK2

Tyrosine-protein kinase JAK2 · UniProt O60674

Length
1132 aa
Mass
130.7 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

JAK2 is a non-receptor tyrosine kinase that constitutively associates with cytokine receptors and transduces ligand-induced receptor engagement into downstream STAT signaling, governing hematopoiesis, metabolism, and cell differentiation (PMID:7508935, PMID:30044226). It is pre-assembled on receptors such as the prolactin, erythropoietin, leptin, and growth hormone receptors and is activated by ligand-induced receptor dimerization: crystallographic and single-molecule data show that a membrane-proximal receptor 'switch' region drives JAK2 FERM-domain dimerization, while reorientation of the receptor relieves pseudokinase (JH2) domain–mediated autoinhibition to permit trans-phosphorylation between kinase domains (PMID:30044226, PMID:38457493, PMID:25656053). The SH2–pseudokinase linker relays this signal, and lesions in the linker or pseudokinase hinge yield constitutive, ligand-independent activation (PMID:19638629). Once active, JAK2 phosphorylates STAT5 through a kinase-domain/SH2 interaction (PMID:9575217), and an expanding substrate repertoire including histone H3 at Tyr41—which displaces HP1alpha to derepress chromatin target genes such as lmo2 (PMID:19783980), the dioxygenase TET2 at Y1939/Y1964 (linking JAK2 to DNA hydroxymethylation via KLF1) (PMID:30944118), PAK1 (PMID:17726028), and the mRNA-processing factor YBX1 (PMID:33239784). JAK2 also acts as a kinase-independent scaffold to support STAT3 phosphorylation by Src-family kinases (PMID:18718905). Its activity is restrained by PTP1B-mediated dephosphorylation (PMID:11694501), inhibitory Ser523 phosphorylation (PMID:16705160), and ARID2-directed NEDD4L-mediated ubiquitination and degradation (PMID:36396719). Gain-of-function lesions—the V617F and exon 12 (e.g. K539L) mutations in/around JH2, and the TEL-JAK2 fusion—cause constitutive kinase activation and myeloproliferative or leukemic disease, and JAK2 is pharmacologically targetable at both its ATP pocket and its JH2 domain (PMID:38457493, PMID:17267906, PMID:10845925, PMID:32329617).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 High

    Established that JAK2 is a pre-assembled receptor-associated kinase rather than a recruited effector, answering how cytokine receptors lacking intrinsic catalytic activity transduce signals.

    Evidence Reciprocal anti-JAK2/anti-phosphotyrosine Co-IP and in vitro kinase assay on the prolactin receptor

    PMID:7508935

    Open questions at the time
    • Did not resolve the structural basis of receptor association
    • Mechanism of activation upon ligand binding not defined
  2. 1998 High

    Mapped the JAK2 kinase domain as sufficient for STAT5 engagement and identified the pseudokinase domain as autoinhibitory, framing JH2 as a brake on catalytic activity.

    Evidence Reconstituted Jak2-Stat5 system in yeast with deletion/point mutagenesis and reporter assays

    PMID:9575217

    Open questions at the time
    • Structural mechanism of JH2 autoinhibition unresolved
    • Did not test physiological receptor context
  3. 2000 High

    Demonstrated that constitutive JAK2 kinase activation is oncogenic, by showing the TEL-JAK2 fusion drives growth-factor independence and leukemia.

    Evidence In vitro kinase assay, Ba/F3 proliferation, and transgenic mouse leukemia model with STAT activation

    PMID:10845925

    Open questions at the time
    • Native point-mutation drivers not yet identified
    • STAT-independent contributions not dissected
  4. 2001 High

    Identified the first direct negative regulator of JAK2, showing PTP1B dephosphorylates JAK2 to terminate cytokine signaling.

    Evidence Substrate-trapping Co-IP, in vitro phosphatase assay, and PTP1B-knockout MEFs

    PMID:11694501

    Open questions at the time
    • Spatial/temporal control of PTP1B-JAK2 encounter unknown
    • Relative contribution versus other phosphatases unclear
  5. 2006 High

    Revealed serine phosphorylation as a distinct off-switch, with Ser523 phosphorylation independently restraining JAK2-dependent leptin signaling.

    Evidence Mass spectrometry site identification and S523A mutagenesis with LRb signaling readouts

    PMID:16705160

    Open questions at the time
    • Kinase responsible for Ser523 phosphorylation not identified
    • Mechanism by which Ser523 modulates catalysis unknown
  6. 2007 High

    Expanded the JAK2 substrate repertoire beyond STATs (PAK1) and confirmed exon 12 mutations as bona fide myeloproliferative drivers distinct from V617F.

    Evidence In vitro kinase assays with MS site mapping for PAK1; biochemical and bone-marrow-transplant models for exon 12 K539L

    PMID:17267906 PMID:17726028

    Open questions at the time
    • Cellular contexts where PAK1 phosphorylation is relevant not fully defined
    • Why exon 12 mutations preferentially cause erythrocytosis unresolved
  7. 2008 High

    Uncovered a kinase-independent scaffolding role for JAK2 and a tissue role in myogenic differentiation, broadening JAK2 function beyond direct phosphotransfer.

    Evidence JAK2-null cells with Src inhibitors/dominant-negatives and kinase-inactive JAK2; JAK2 inhibitor/siRNA in myoblast differentiation assays

    PMID:18718905 PMID:18835816

    Open questions at the time
    • Structural basis of scaffolding function not defined
    • Myogenic role relies in part on inhibitor specificity (Medium)
  8. 2009 High

    Established a direct nuclear/chromatin function for JAK2, showing it phosphorylates histone H3Y41 to displace HP1alpha and derepress target genes, and refined the activation switch to the SH2-pseudokinase linker.

    Evidence In vitro kinase assay, ChIP, and inhibitor treatment for H3Y41; scanning mutagenesis and erythrocytosis mouse model for the linker switch

    PMID:19638629 PMID:19783980

    Open questions at the time
    • How nuclear JAK2 is targeted to specific loci unknown
    • Breadth of chromatin targets beyond lmo2 not mapped
  9. 2018 High

    Provided the structural basis for activation, showing receptor switch-region-mediated 2:2 JAK2/receptor dimerization is required to trigger kinase activation.

    Evidence X-ray crystallography of JAK2 FERM-SH2 with LEPR and EPOR plus switch-region mutagenesis and STAT phosphorylation assays

    PMID:30044226

    Open questions at the time
    • Full-length receptor-JAK2 complex architecture not resolved
    • Dynamics of JH2 disengagement not directly visualized
  10. 2019 High

    Connected JAK2 signaling to epigenetic control, showing it directly phosphorylates and activates TET2 to alter DNA hydroxymethylation, with implications for V617F-driven disease.

    Evidence Phosphoproteomics, in vitro kinase assay, Co-IP of TET2-KLF1, 5hmC quantification in patient samples and mouse models

    PMID:30944118

    Open questions at the time
    • Genome-wide consequences of TET2 activation incompletely defined
    • Crosstalk with TET2 loss-of-function mutations unclear
  11. 2020 High

    Identified YBX1 as a mutant-JAK2 substrate enabling clonal persistence and validated the pseudokinase domain as a druggable site, opening therapeutic strategies against JAK-inhibitor-resistant disease.

    Evidence Phosphoproteomics with YBX1 genetic inactivation, RNA-seq, and in vivo models; JH2-selective ligand crystal structures with STAT5 cellular assays

    PMID:32329617 PMID:33239784

    Open questions at the time
    • Mechanistic link between YBX1 phosphorylation and splicing/ERK control incomplete
    • In vivo efficacy of JH2-selective inhibitors not established
  12. 2021 High

    Delivered structural detail on inhibitor binding at the ATP pocket and placed JAK2 within IL-6/gp130/STAT3 signaling driving sepsis-associated muscle atrophy.

    Evidence Crystal structures with ruxolitinib/fedratinib plus biochemical/cellular assays; JAK2 inhibitor and gp130 knockdown in sepsis mouse and C2C12 models

    PMID:33570945 PMID:34821076

    Open questions at the time
    • Atrophy pathway placement relies on inhibitor specificity (Medium)
    • Selectivity determinants versus other JAK family members not addressed
  13. 2022 High

    Defined a transcription-coupled degradation axis controlling JAK2 abundance, in which ARID2 drives NEDD4L-mediated JAK2 ubiquitination and loss of this control promotes hepatic steatosis.

    Evidence ChIP, ubiquitination and Co-IP assays, liver-specific Arid2 knockout and HFD mice with JAK2 inhibitor rescue

    PMID:36396719

    Open questions at the time
    • Direct NEDD4L-JAK2 recognition determinants not mapped
    • Generalizability beyond liver unclear
  14. 2024 High

    Mechanistically distinguished how different oncogenic pseudokinase mutations activate JAK2, linking receptor dimerization, increased catalysis, and loss of autoinhibition; also placed JAK2 in PF4/c-Mpl platelet signaling.

    Evidence qSMLM of EpoR dimerization, crystallography, kinase assays and MD simulations for V617F/K539L/R683S; binding and platelet aggregation assays for PF4/c-Mpl/JAK2/STAT

    PMID:37883794 PMID:38457493

    Open questions at the time
    • Quantitative contribution of dimerization versus intrinsic activity per mutant not fully reconciled
    • PF4/c-Mpl axis lacks structural detail (Medium)

Open questions

Synthesis pass · forward-looking unresolved questions
  • How nuclear JAK2 is recruited to specific chromatin loci and how its kinase-independent scaffolding versus catalytic functions are coordinated across tissues remains unresolved.
  • No mechanism for locus-specific nuclear targeting
  • Scaffolding versus catalytic role partitioning undefined
  • Integration of the full substrate network (STAT, TET2, PAK1, YBX1, H3) not modeled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016740 transferase activity 4 GO:0060089 molecular transducer activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2 R-HSA-392499 Metabolism of proteins 1 R-HSA-4839726 Chromatin organization 1
Partners
EPORLEPRMPLNEDD4LPRLRPTP1BSH2B1STAT5

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 JAK2 is present in the nucleus of haematopoietic cells and directly phosphorylates histone H3 at Tyr41 (H3Y41). This phosphorylation prevents binding of HP1alpha (but not HP1beta) to H3 via its chromo-shadow domain. Inhibition of JAK2 decreases H3Y41 phosphorylation and lmo2 expression at its promoter while increasing HP1alpha binding at the same site. In vitro kinase assay, nuclear fractionation, ChIP, JAK2 inhibitor treatment in leukemic cells, immunoprecipitation Nature High 19783980
2001 JAK2 (and TYK2) are direct substrates of protein-tyrosine phosphatase PTP1B. PTP1B recognizes the consensus (E/D)-pY-pY-(R/K) motif in JAK2, similar to the insulin receptor dephosphorylation site. A substrate-trapping PTP1B mutant formed stable complexes with JAK2 upon interferon stimulation, and PTP1B expression or trapping mutant inhibited interferon-dependent transcriptional activation. PTP1B-deficient MEFs displayed hyperphosphorylation of JAK2. Substrate-trapping mutant co-immunoprecipitation, in vitro phosphatase assay, PTP1B knockout MEFs, interferon-dependent transcriptional activation assay The Journal of biological chemistry High 11694501
1994 JAK2 is constitutively associated with the prolactin receptor (PRLR) and undergoes rapid tyrosine phosphorylation and kinase activation in response to prolactin binding. JAK2 association with PRLR was present before and after ligand binding, indicating JAK2 is a pre-assembled receptor-associated kinase that is activated by ligand-induced receptor activation. Reciprocal anti-JAK2/anti-phosphotyrosine immunoprecipitation, in vitro tyrosine kinase assay with [gamma-32P]ATP, phosphoamino acid analysis, anti-receptor immunoprecipitation followed by anti-JAK2 immunoblotting The Journal of biological chemistry High 7508935
2018 Crystal structures of JAK2 FERM and SH2 domains bound to leptin receptor (LEPR) and erythropoietin receptor (EPOR) reveal a dimeric 2:2 JAK2/receptor conformation. A membrane-proximal 'switch' region peptide motif on the receptor is essential for dimer formation. Mutation of the receptor switch region disrupts STAT phosphorylation but does not affect JAK2 binding, demonstrating that receptor-mediated JAK2 FERM dimerization is required for kinase activation. X-ray crystallography, STAT phosphorylation assay, mutagenesis of receptor switch region eLife High 30044226
2009 The SH2-pseudokinase domain linker of JAK2 acts as a switch that relays cytokine receptor engagement signals to kinase activation. The N-terminal part of the linker is essential for interaction of JAK2 with the Epo receptor, while mutations in the C-terminal region confer constitutive activation. Mutations of Glu543-Asp544 in the linker or Leu611, Arg683, or Phe694 in the pseudokinase domain hinge region yield constitutively active JAK2 that cannot be further stimulated by Epo. Functional gain-of-function screen, scanning mutagenesis, erythrocytosis mouse model, in vitro receptor-binding assay The Journal of biological chemistry High 19638629
2007 JAK2 directly phosphorylates PAK1 at tyrosines 153, 201, and 285 in vivo and in vitro. Tyrosyl phosphorylation by JAK2 significantly increases PAK1 kinase activity. This phosphorylation decreases apoptosis induced by serum deprivation and staurosporine and increases cell motility. A triple PAK1 Y153F/Y201F/Y285F mutant was unaffected by JAK2-mediated phosphorylation. In vitro kinase assay, mass spectrometry, 2D peptide mapping, site-directed mutagenesis, apoptosis assay, cell motility assay The Journal of biological chemistry High 17726028
2019 Cytokine receptor-associated JAK2 phosphorylates TET2 at tyrosines Y1939 and Y1964, leading to TET2 activation and increased DNA hydroxymethylation. Phosphorylated TET2 interacts with the erythroid transcription factor KLF1, and this interaction increases upon erythropoietin exposure. The activating JAK2V617F mutation is associated with increased TET2 activity and genome-wide loss of cytosine methylation. Phosphoproteomics, in vitro kinase assay, Co-IP, 5-hydroxymethylcytosine quantification, bisulfite sequencing, patient samples and mouse models Cancer discovery High 30944118
2006 Phosphorylation of JAK2 on Ser523 inhibits JAK2-dependent leptin receptor (LRb) signaling. Ser523 is phosphorylated in intact cells and in mouse spleen independently of LRb-JAK2 activation. Mutation S523A sensitizes and prolongs JAK2 signaling following LRb activation, and the inhibitory effect is independent of Tyr570-mediated inhibition. Tandem mass spectrometric phosphorylation site identification, site-directed mutagenesis (S523A), LRb signaling assays in cells Molecular and cellular biology High 16705160
1998 Jak2 kinase domain (JH1) alone is sufficient for interaction with and phosphorylation of Stat5. Deletion of the pseudokinase domain (JH2) causes increased enzymatic activity of Jak2. A Stat5 SH2 domain R618K mutation abolishes phosphorylation by Jak2. A single phosphotyrosine-SH2 domain interaction is sufficient for Stat5 dimerization but such dimers bind DNA inefficiently. Yeast two-hybrid/functional system with Jak2 and Stat5, co-immunoprecipitation under stringent conditions, deletion/point mutagenesis, Stat-dependent reporter gene assay The Journal of biological chemistry High 9575217
2024 Quantitative superresolution microscopy showed that EpoR exists as monomers and dimerizes upon Epo stimulation or through JAK2 pseudokinase domain mutations (V617F, K539L, R683S). Crystallographic analysis with kinase activity assays revealed distinct activation mechanisms: JAK2 V617F activity is driven by dimerization; K539L involves both increased receptor dimerization and kinase activity; R683S prevents autoinhibition, increases catalytic activity, and drives JAK2 equilibrium toward the activation state through a wild-type dimer interface. Quantitative single-molecule localization microscopy (qSMLM), X-ray crystallography, in vitro kinase activity assay, molecular dynamics simulations, AI-guided structural modeling Science advances High 38457493
2021 In the context of sepsis, the IL-6/gp130/JAK2/STAT3 pathway mediates muscle atrophy. JAK2 inhibition (AG490) reduces STAT3 phosphorylation and attenuates muscle atrophy in septic mice, accompanied by reduction in Fbxo32/Atrogin-1 and Trim63/MuRF1 mRNA and protein expression. In C2C12 myotubes, JAK2 inhibition decreases IL-6-induced Socs3 mRNA expression and myotube atrophy. JAK2 inhibitor (AG490) treatment in CLP sepsis mouse model, siRNA knockdown of Il6st/gp130, STAT3 phosphorylation assays, muscle weight/atrophy phenotype, RNAseq Journal of cachexia, sarcopenia and muscle Medium 34821076
2020 In-depth phosphoproteome profiling of JAK2-mutant cells identified YBX1, an mRNA-processing protein, as a post-translationally modified target of mutant JAK2. JAK2-dependent phosphorylation of YBX1 maintains its function in RNA splicing and transcriptional control of ERK signaling, enabling persistence of JAK2V617F malignant clones despite JAK inhibitor treatment. YBX1 inactivation combined with JAK inhibition causes apoptosis of JAK2-dependent cells and molecular remission in vivo. Phosphoproteomics, genetic inactivation of YBX1, RNA-seq (splicing analysis), in vivo mouse models, primary human cells, apoptosis assays Nature High 33239784
2007 JAK2 exon 12 gain-of-function mutations (including K539L substitution) result in increased phosphorylation of JAK2 and ERK1/2 compared to wild-type or V617F JAK2. BaF3 cells expressing exon 12 mutant JAK2 proliferate without IL-3. K539L JAK2 induces a myeloproliferative phenotype including erythrocytosis in a murine retroviral bone marrow transplantation model. Biochemical phosphorylation assays in BaF3 cells, murine bone marrow transplantation, cytokine-independent proliferation assay The New England journal of medicine High 17267906
2000 The TEL-JAK2 fusion protein, in which the TEL self-association domain is fused to the JAK2 kinase domain, exhibits constitutive activation of tyrosine kinase activity and confers growth factor-independent proliferation to IL-3-dependent Ba/F3 cells. Expression in transgenic mice under a lymphoid promoter causes fatal T-cell leukemia with activation of STAT1 and STAT5. In vitro kinase assay, Ba/F3 proliferation assay, transgenic mouse model, immunoblotting for STAT activation Blood High 10845925
2008 JAK2/STAT2/STAT3 pathway is required for early myogenic differentiation. Inhibition of JAK2 (by small molecule inhibitor or siRNA) blocks myogenic differentiation of myoblasts. JAK2, STAT2, and STAT3 are activated upon differentiation induction. The pro-differentiation effect is partially mediated by MyoD and MEF2, and JAK2/STAT2/STAT3 regulates expression of IGF2 and HGF genes. Small molecule JAK2 inhibitor, siRNA knockdown, differentiation assays, immunoblotting for pathway activation The Journal of biological chemistry Medium 18835816
2021 Crystal structures of JAK2 bound to ruxolitinib and fedratinib (and derivatives) were determined from mammalian cell-produced JAK2, providing structural basis for inhibitor binding including shape complementarity requirements for chiral and achiral inhibitors at the ATP-binding pocket. X-ray crystallography, biochemical kinase assay, cellular activity assays Journal of medicinal chemistry High 33570945
2020 Five crystal structures of the JAK2 pseudokinase domain (JH2) complexed with selective diaminotriazole ligands were determined. Selective JH2 binders (over kinase domain JH1) inhibit STAT5 phosphorylation in cells expressing both wild-type and V617F JAK2, demonstrating that JH2 is a pharmacologically targetable domain that modulates JAK2 activity. X-ray crystallography (5 structures), binding affinity measurements for JH1/JH2/JH2-V617F, STAT5 phosphorylation cellular assay Journal of medicinal chemistry High 32329617
2022 ARID2 promotes ubiquitination and degradation of JAK2 via the E3 ubiquitin ligase NEDD4L. ARID2 recruits CARM1 to increase H3R17me2a at the NEDD4L promoter, activating NEDD4L transcription. Loss of ARID2 stabilizes JAK2, activating JAK2-STAT5-PPARγ signaling and inducing hepatic steatosis. Fedratinib (JAK2 inhibitor) alleviated HFD-induced hepatic steatosis in liver-specific Arid2 KO mice. ChIP assay, ubiquitination assay, Co-IP, liver-specific Arid2 knockout mice, HFD mouse model, JAK2 inhibitor treatment, immunoblotting Cell death and differentiation High 36396719
2024 PF4 (platelet factor 4) binds and activates the thrombopoietin receptor c-Mpl on platelets, leading to JAK2 activation and phosphorylation of STAT3 and STAT5, resulting in platelet aggregation. Inhibition of the c-Mpl-JAK2 pathway inhibits platelet aggregation to PF4 and to VITT sera. Binding assay, JAK2 pathway inhibition (pharmacological), STAT3/STAT5 phosphorylation assays, platelet aggregation assay Blood Medium 37883794
2015 A model for JAK2 activation by the GH receptor homodimer was established based on biochemical data and molecular dynamics simulations: constitutive receptor dimers undergo ligand-induced reorientation/rotation, transitioning from parallel to separated transmembrane domains. This movement slides the pseudokinase inhibitory domain of one JAK2 away from the kinase domain of the other JAK2 within the dimer, allowing trans-activation between kinase domains. Biochemical receptor dimerization assays, molecular dynamics simulations The Biochemical journal Medium 25656053
2008 Leptin stimulates JAK2-independent STAT3 phosphorylation via non-JAK2 tyrosine kinases including Src family members (c-Src, Fyn) downstream of LEPRb. JAK2 mediates leptin signaling both by phosphorylating substrates and by serving as a scaffolding/adaptor protein. Kinase-inactive JAK2(K882E) is tyrosyl-phosphorylated by non-JAK2 kinases in JAK2-null cells and enhances STAT3 phosphorylation, indicating a scaffolding role. JAK2-null cell lines (human and mouse), pharmacological Src inhibitors, dominant negative Src(K298M), overexpression of c-Src/Fyn, kinase-inactive JAK2 mutant, LEPRb Tyr mutants The Journal of biological chemistry High 18718905
2000 SH2-B binds with high affinity via its SH2 domain to phosphorylated tyrosines within JAK2 in response to GH. GH-induced binding of SH2-B to JAK2 potently activates JAK2, leading to enhanced tyrosyl phosphorylation of STAT proteins and other cellular proteins. SIRP binds directly to JAK2 without requiring tyrosyl phosphorylation, is itself phosphorylated on tyrosines in response to GH, and recruits SHP2 which dephosphorylates SIRP and likely JAK2, acting as a negative regulator. Co-immunoprecipitation, in vitro binding/kinase assays, STAT phosphorylation assays, SH2 domain binding studies Recent progress in hormone research Medium 11036942

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. The New England journal of medicine 1430 24325359
2010 Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. The New England journal of medicine 982 20843246
2007 JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. The New England journal of medicine 982 17267906
2009 JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature 482 19783980
2007 Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. Nature reviews. Cancer 453 17721432
2001 TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B. The Journal of biological chemistry 381 11694501
1994 Activation of receptor-associated tyrosine kinase JAK2 by prolactin. The Journal of biological chemistry 293 7508935
2018 Macrophage Inflammation, Erythrophagocytosis, and Accelerated Atherosclerosis in Jak2 V617F Mice. Circulation research 230 30571460
2013 Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis. Leukemia 204 23459451
2019 Roles of JAK2 in Aging, Inflammation, Hematopoiesis and Malignant Transformation. Cells 200 31398915
2021 Sepsis induces interleukin 6, gp130/JAK2/STAT3, and muscle wasting. Journal of cachexia, sarcopenia and muscle 178 34821076
2018 The JAK2 pathway is activated in idiopathic pulmonary fibrosis. Respiratory research 166 29409529
2020 Splicing factor YBX1 mediates persistence of JAK2-mutated neoplasms. Nature 131 33239784
2008 JAK2/STAT2/STAT3 are required for myogenic differentiation. The Journal of biological chemistry 121 18835816
2011 The JAK2 exon 12 mutations: a comprehensive review. American journal of hematology 119 21674578
2007 Jak2: normal function and role in hematopoietic disorders. Current opinion in genetics & development 114 17208428
2000 TEL-JAK2 transgenic mice develop T-cell leukemia. Blood 103 10845925
2015 JAK2 activation by growth hormone and other cytokines. The Biochemical journal 102 25656053
2005 A JAK2 mutation in myeloproliferative disorders: pathogenesis and therapeutic and scientific prospects. Trends in molecular medicine 94 16271512
2017 JAK2 inhibitors for myeloproliferative neoplasms: what is next? Blood 89 28500170
2008 JAK2 and MPL mutations in myeloproliferative neoplasms: discovery and science. Leukemia 85 18754026
2021 Structural Insights into JAK2 Inhibition by Ruxolitinib, Fedratinib, and Derivatives Thereof. Journal of medicinal chemistry 81 33570945
2009 Therapeutic potential of JAK2 inhibitors. Hematology. American Society of Hematology. Education Program 81 20008249
2012 MiR-135a targets JAK2 and inhibits gastric cancer cell proliferation. Cancer biology & therapy 80 22310976
2018 Mechanistic Insights into Regulation of JAK2 Tyrosine Kinase. Frontiers in endocrinology 76 29379470
2008 Leptin stimulates both JAK2-dependent and JAK2-independent signaling pathways. The Journal of biological chemistry 75 18718905
2018 Tumor CDKN2A-Associated JAK2 Loss and Susceptibility to Immunotherapy Resistance. Journal of the National Cancer Institute 69 29917141
2015 Molecular insights into regulation of JAK2 in myeloproliferative neoplasms. Blood 59 25824690
2010 JAK2 inhibitors: what's the true therapeutic potential? Blood reviews 56 21095048
2018 Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR-375/JAK2. Immunology and cell biology 54 30302825
2014 Effects of JAK2-STAT3 signaling after cerebral insults. JAK-STAT 52 25105066
2019 Cytokine-Regulated Phosphorylation and Activation of TET2 by JAK2 in Hematopoiesis. Cancer discovery 51 30944118
2014 JAK2 and MPL protein levels determine TPO-induced megakaryocyte proliferation vs differentiation. Blood 50 25143485
2022 DUSP6 mediates resistance to JAK2 inhibition and drives leukemic progression. Nature cancer 48 36581736
2018 Receptor-mediated dimerization of JAK2 FERM domains is required for JAK2 activation. eLife 48 30044226
2008 The JAK2 V617F mutation and thrombosis. British journal of haematology 47 19004076
2006 Phosphorylation of Jak2 on Ser(523) inhibits Jak2-dependent leptin receptor signaling. Molecular and cellular biology 47 16705160
2024 JAK2-mutant clonal hematopoiesis is associated with venous thromboembolism. Blood 46 39102652
2007 JAK-2 mutations and their relevance to myeloproliferative disease. Current opinion in hematology 45 17133099
2007 JAK2 tyrosine kinase phosphorylates PAK1 and regulates PAK1 activity and functions. The Journal of biological chemistry 45 17726028
2000 Role of the tyrosine kinase JAK2 in signal transduction by growth hormone. Pediatric nephrology (Berlin, Germany) 45 10912517
2023 JAK2 unmutated erythrocytosis: 2023 Update on diagnosis and management. American journal of hematology 44 36966432
2020 Inhibition of JAK2 Suppresses Myelopoiesis and Atherosclerosis in Apoe-/- Mice. Cardiovascular drugs and therapy 44 32086626
2013 JAK2 mutation-related disease and thrombosis. Seminars in thrombosis and hemostasis 44 23633193
2020 Platelet Dysfunction and Thrombosis in JAK2V617F-Mutated Primary Myelofibrotic Mice. Arteriosclerosis, thrombosis, and vascular biology 42 32814440
2006 JAK2 V617F in myeloid disorders: what do we know now, and where are we headed? Leukemia & lymphoma 42 16321848
2004 Jak2 tyrosine kinase: a true jak of all trades? Cell biochemistry and biophysics 42 15475610
2013 Inhibitors of JAK2 and JAK3: an update on the patent literature 2010 - 2012. Expert opinion on therapeutic patents 41 23367873
2017 Mechanisms of Resistance to JAK2 Inhibitors in Myeloproliferative Neoplasms. Hematology/oncology clinics of North America 40 28673392
1998 Jak2-Stat5 interactions analyzed in yeast. The Journal of biological chemistry 40 9575217
2022 Interleukin-29 Accelerates Vascular Calcification via JAK2/STAT3/BMP2 Signaling. Journal of the American Heart Association 38 36537334
2009 A JAK2 interdomain linker relays Epo receptor engagement signals to kinase activation. The Journal of biological chemistry 38 19638629
2022 JAK2 in Myeloproliferative Neoplasms: Still a Protagonist. Pharmaceuticals (Basel, Switzerland) 37 35215273
2013 JAK2-STAT5B pathway and osteoblast differentiation. JAK-STAT 37 24470975
2024 PF4 activates the c-Mpl-Jak2 pathway in platelets. Blood 36 37883794
2023 FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma. BMC cancer 36 36814203
2021 JAK2-mediated Intracellular Signaling. Current molecular medicine 36 33059575
2019 Curcumin induces apoptosis in JAK2-mutated cells by the inhibition of JAK2/STAT and mTORC1 pathways. Journal of cellular and molecular medicine 35 31033209
2013 Sensitivity and resistance of JAK2 inhibitors to myeloproliferative neoplasms. International journal of hematology 35 23670175
2012 Ruxolitinib, an oral JAK1 and JAK2 inhibitor, in myelofibrosis. Expert opinion on pharmacotherapy 34 23051187
2010 Recent developments on JAK2 inhibitors: a patent review. Expert opinion on therapeutic patents 34 20205617
2017 JAK2 variations and functions in lung adenocarcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 33 28639892
2017 CD274 (PDL1) and JAK2 genomic amplifications in pulmonary squamous-cell and adenocarcinoma patients. Histopathology 33 28795418
2005 The V617F JAK2 mutation and the myeloproliferative disorders. Hematological oncology 33 16285006
2021 JAK2 regulates paclitaxel resistance in triple negative breast cancers. Journal of molecular medicine (Berlin, Germany) 29 34626199
2015 CXCL12 Regulates through JAK1 and JAK2 Formation of Productive Immunological Synapses. Journal of immunology (Baltimore, Md. : 1950) 29 25917087
2007 JAK2 mutations and clinical practice in myeloproliferative neoplasms. Cancer journal (Sudbury, Mass.) 29 18032973
2000 SH2-B and SIRP: JAK2 binding proteins that modulate the actions of growth hormone. Recent progress in hormone research 29 11036942
2019 Recurrent PTPRT/JAK2 mutations in lung adenocarcinoma among African Americans. Nature communications 28 31844068
2012 JAK2 inhibition for the treatment of hematologic and solid malignancies. Expert opinion on investigational drugs 28 22493978
2009 Prospect of JAK2 inhibitor therapy in myeloproliferative neoplasms. Expert review of anticancer therapy 28 19445582
2018 JAK2 is dispensable for maintenance of JAK2 mutant B-cell acute lymphoblastic leukemias. Genes & development 27 29907650
2016 JAK2V617F-mutant vascular niche contributes to JAK2V617F clonal expansion in myeloproliferative neoplasms. Blood cells, molecules & diseases 27 27865175
2014 Myeloproliferative neoplasms: JAK2 signaling pathway as a central target for therapy. Clinical lymphoma, myeloma & leukemia 27 25486952
2022 JAK2 inhibitor persistence in MPN: uncovering a central role of ERK activation. Blood cancer journal 24 35082276
2022 SPP1 promotes radiation resistance through JAK2/STAT3 pathway in esophageal carcinoma. Cancer medicine 24 35593388
2020 Selective Janus Kinase 2 (JAK2) Pseudokinase Ligands with a Diaminotriazole Core. Journal of medicinal chemistry 24 32329617
2011 Nuclear JAK2: form and function in cancer. Anatomical record (Hoboken, N.J. : 2007) 24 21809458
2009 Jak2 inhibitors: rationale and role as therapeutic agents in hematologic malignancies. Current oncology reports 22 19216843
2007 JAK2 V617F: implications for thrombosis in myeloproliferative diseases. Current opinion in hematology 22 17934351
2006 JAK2, the JAK2 V617F mutant and cytokine receptors. Pathologie-biologie 22 16904848
2010 JAK2 mutation and thrombosis in the myeloproliferative neoplasms. Current hematologic malignancy reports 21 20425393
2023 Iron is a modifier of the phenotypes of JAK2-mutant myeloproliferative neoplasms. Blood 20 36758212
2012 Targeting JAK2 in the therapy of myeloproliferative neoplasms. Expert opinion on therapeutic targets 20 22339244
2022 Curcumol Attenuates Endometriosis by Inhibiting the JAK2/STAT3 Signaling Pathway. Medical science monitor : international medical journal of experimental and clinical research 18 35279667
2019 TG101348, a selective JAK2 antagonist, ameliorates hepatic fibrogenesis in vivo. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 31100032
2015 Oncogenic Drivers in Myeloproliferative Neoplasms: From JAK2 to Calreticulin Mutations. Current hematologic malignancy reports 18 26370832
2012 JAK2 inhibitors for myelofibrosis: why are they effective in patients with and without JAK2V617F mutation? Anti-cancer agents in medicinal chemistry 18 22583424
2011 New JAK2 inhibitors for myeloproliferative neoplasms. Expert opinion on investigational drugs 18 21521147
2008 The role of JAK2 mutations in RARS and other MDS. Hematology. American Society of Hematology. Education Program 18 19074058
2022 Macrophage Jak2 deficiency accelerates atherosclerosis through defects in cholesterol efflux. Communications biology 17 35169231
2019 Cooperative Blockade of PKCα and JAK2 Drives Apoptosis in Glioblastoma. Cancer research 17 31806641
2014 Dual Aurora A and JAK2 kinase blockade effectively suppresses malignant transformation. Oncotarget 17 24930769
2024 Molecular basis of JAK2 activation in erythropoietin receptor and pathogenic JAK2 signaling. Science advances 16 38457493
2022 Insights on JAK2 Modulation by Potent, Selective, and Cell-Permeable Pseudokinase-Domain Ligands. Journal of medicinal chemistry 16 35653642
2022 LPCAT1 functions as an oncogene in cervical cancer through mediating JAK2/STAT3 signaling. Experimental cell research 16 36122769
2022 ARID2 mitigates hepatic steatosis via promoting the ubiquitination of JAK2. Cell death and differentiation 16 36396719
2018 The JAK2 GGCC (46/1) Haplotype in Myeloproliferative Neoplasms: Causal or Random? International journal of molecular sciences 16 29641446
2016 The Relevance of JAK2 in the Regulation of Cellular Transport. Current medicinal chemistry 16 26639094
2014 Pyrrole-3-carboxamides as potent and selective JAK2 inhibitors. Bioorganic & medicinal chemistry 16 25009002

Missed literature

Know a paper Affinage missed for JAK2? Flag it for the maintainers and the community.

No submissions yet.