JAK2 Monoclonal Antibody

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Description

Introduction to JAK2 and Monoclonal Antibodies

JAK2 is a tyrosine kinase involved in signaling through cytokine receptors (e.g., erythropoietin, thrombopoietin). Mutations such as JAK2 V617F drive myeloproliferative neoplasms (MPNs) like myelofibrosis and polycythemia vera . Monoclonal antibodies are engineered to bind specific epitopes of JAK2, enabling precise detection or neutralization.

Key Features:

  • Specificity: Engineered to avoid cross-reactivity with JAK1, JAK3, or Tyk2 .

  • Applications: Western blot (WB), immunofluorescence (IF), immunoprecipitation (IP), and immunohistochemistry (IHC) .

  • Therapeutic Potential: Targeting mutant JAK2 (e.g., JAK2 V617F) in MPNs .

Applications in Research and Diagnostics

JAK2 monoclonal antibodies are widely used to study JAK2 expression, phosphorylation, and signaling pathways.

Table 1: Key Applications

ApplicationDescriptionAntibody Example (Clone)Source
Western BlotDetect JAK2 protein levels in cell lysates.MA5-15632 (1C1)
ImmunofluorescenceVisualize JAK2 localization in cells (e.g., A549 lung cancer cells).M00027
ImmunohistochemistryAssess JAK2 expression in tissue samples (e.g., rheumatoid arthritis).JAK2-specific polyclonal
ImmunoprecipitationStudy JAK2 interactions with signaling molecules (e.g., STAT proteins).EPR108(2)

Notable Research Findings:

  • Rheumatoid Arthritis: JAK2 expression is elevated in inflammatory cells (macrophages, neutrophils) and mast cells in rat adjuvant-induced arthritis models .

  • Cancer Biology: JAK2 antibodies confirm JAK2 overexpression in myeloid malignancies and its role in STAT5 activation .

Key JAK2 Monoclonal Antibodies

Several antibodies are validated for research, each with distinct characteristics.

Therapeutic Potential and Clinical Relevance

While JAK2 inhibitors (e.g., ruxolitinib) dominate MPN treatment, monoclonal antibodies offer complementary mechanisms:

Mechanisms of Action:

  1. Targeted Depletion: Antibodies bind mutant JAK2 (e.g., JAK2 V617F), inducing apoptosis in neoplastic cells .

  2. Immune Modulation: Enhance anti-tumor immunity by blocking PD-L1 expression on MPN cells .

Clinical Insights:

  • Myelofibrosis: A novel monoclonal antibody (preclinical) reduces CALR-mutant cells and improves splenomegaly .

  • MPNs: Deleting JAK2 V617F via dual-recombinase systems depletes mutant hematopoietic stem cells, prolonging survival .

Limitations:

  • Cross-Reactivity: Early antibodies risk binding non-JAK2 kinases (e.g., JAK1) .

  • Delivery Challenges: Systemic administration required for hematologic malignancies.

Challenges and Future Directions

Challenges:

  • Specificity: Avoiding off-target effects on JAK1/3 or other kinases .

  • Resistance: Chronic JAK inhibitor use may select for persistent clones .

Future Directions:

  • Mutant-Selective Antibodies: Targeting JAK2 V617F or CALR mutations .

  • Bispecific Antibodies: Dual targeting of JAK2 and immune checkpoints (e.g., PD-1) .

Product Specs

Buffer
PBS, pH 7.4, containing 0.02% sodium azide as preservative and 50% glycerol.
Form
Liquid
Lead Time
Typically, we can ship products within 1-3 business days of receiving your order. Delivery times may vary based on shipping method and destination. Please consult your local distributor for specific delivery information.
Synonyms
JAK 2 antibody; JAK-2 antibody; JAK2 antibody; JAK2_HUMAN antibody; Janus Activating Kinase 2 antibody; Janus kinase 2 (a protein tyrosine kinase) antibody; Janus kinase 2 antibody; JTK 10 antibody; JTK10 antibody; kinase Jak2 antibody; OTTHUMP00000043260 antibody; THCYT3 antibody; Tyrosine protein kinase JAK2 antibody; Tyrosine-protein kinase JAK2 antibody
Uniprot No.

Target Background

Function
JAK2 (Janus kinase 2) is a non-receptor tyrosine kinase that plays a crucial role in various cellular processes, including growth, development, differentiation, and histone modifications. It mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, JAK2 is involved in signal transduction by associating with type I receptors, such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), and thrombopoietin (THPO), as well as type II receptors, including IFN-alpha, IFN-beta, IFN-gamma, and multiple interleukins. Following ligand binding to cell surface receptors, JAK2 phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs (signal transducer and activator of transcription) proteins. Subsequently, JAK2 phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimers or heterodimers and translocate to the nucleus to activate gene transcription. For instance, during erythropoiesis, cell stimulation with erythropoietin (EPO) leads to JAK2 autophosphorylation, activation, and its association with the erythropoietin receptor (EPOR), which becomes phosphorylated in its cytoplasmic domain. Subsequently, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated, and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. JAK2 also participates in a signaling cascade activated by increased cellular retinol, leading to the activation of STAT5 (STAT5A or STAT5B). Additionally, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. It plays a role in the cell cycle by phosphorylating CDKN1B. JAK2 cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. Within the nucleus, JAK2 plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin.
Gene References Into Functions
  1. Clonal analysis reveals that the dominant JAK2 V617F-positive clone in Polycythemia Vera harbors EGFR C329R substitution, suggesting this mutation may contribute to clonal expansion. PMID: 28550306
  2. Patients with CALR mutation exhibited significantly higher concentrations of PDGF-BB and lower concentrations of SDF-1alpha compared to patients with JAK2V617F mutation. The elevated PDGF-BB and reduced SDF-1alpha levels in CALR(+) ET patients might indicate a role of these chemokines in the disturbed Ca2+ metabolism in platelets. PMID: 29390868
  3. This research presents two crystal structures of the human JAK2 FERM and SH2 domains bound to Leptin receptor (LEPR) and Erythropoietin receptor (EPOR), identifying a novel dimeric conformation for JAK2. PMID: 30044226
  4. This study investigates the pathogenesis mechanism of JAK2 F556V mutation in the MPNs. PMID: 29842959
  5. Mir-204 attenuates angiogenesis in lung adenocarcinoma via the JAK2-STAT3 pathway. PMID: 29281186
  6. FEZF1-AS1 acts as an oncogenic lncRNA in human hepatocellular carcinoma by promoting JAK2/STAT3 signaling-mediated epithelial mesenchymal transformation. PMID: 29957463
  7. Case Reports/Review: JAK2 mutation-associated cerebral arterial infarction and cerebral and systemic venous thromboembolism. PMID: 30056970
  8. HSP27 is a partner of JAK2-STAT5 and a potential therapeutic target in myelofibrosis. PMID: 29650953
  9. This study suggests that the JAK2V617F mutation may increase the risk of thrombosis in chronic myeloproliferative neoplasms. PMID: 30004057
  10. Progression to polycythemia vera from familial thrombocytosis with germline JAK2 R867Q mutation. PMID: 29368262
  11. JAK2 and STAT3 are activated in Idiopathic pulmonary fibrosis. PMID: 29409529
  12. The prevalence of CALR mutation in JAK2V617F-negative essential thrombocythemia in this study is 35.7%. HRM is an effective method of detecting CALR mutation and is a more advantageous method of screening for CALR mutation. PMID: 29521158
  13. Comprehensive genomic characterization identified distinct genetic subgroups and provided a classification of myeloproliferative neoplasms based on causal biological mechanisms. Mutations in JAK2, CALR, or MPL are the sole abnormality in 45% of the patients. PMID: 30304655
  14. Findings outlined in this study demonstrate that the inhibition of P16 decreased the growth and metastasis potential of BC cells by inhibiting IL-6/JAK2/STAT3 signaling. PMID: 29388151
  15. MPL-mutated and CALR-mutated essential thrombocythaemia share clinical and histological characteristics, with both genotypes showing higher platelet counts and marked megakaryocytic proliferation compared to JAK2V617F-mutated ET. PMID: 29934356
  16. Results presented here provide insights into understanding how the JAK2 V625F mutation causes myeloproliferative neoplasms and offer information for the development of JAK2 mutation-specific inhibitors. PMID: 29782975
  17. Concomitant presence of JAK2V617F mutation and BCRABL translocation in two patients: A new entity or a variant of myeloproliferative neoplasms. PMID: 29845291
  18. The JAK2 V617F mutation and thrombocytopenia. PMID: 27614229
  19. PBX1 plays an oncogenic role in clear cell renal carcinoma via the JAK2/STAT3 pathway. PMID: 29678569
  20. This study shows that JAK2V617F leads to abnormal expression of numerous proteins at the membrane of circulating PV red blood cells, with overexpression of CALR and persistence of CANX. PMID: 28385780
  21. In 94.9% of PV, 85.5% ET, and 85.2% PMF, authors found mutations in JAK2, MPL, or CALR. 74.9% carried JAK2V617F, 12.3% CALR mutations, 2.1% MPL mutations, and 10.7% were triple negative. PMID: 28990497
  22. Tyrphostin B42 induced apoptosis of pancreatic cancer cells (PCCs) by regulating the expression of mitochondrial-related genes. Therefore, these findings demonstrated that tyrphostin B42 attenuated trichostatin A resistance in PCCs by antagonizing the IL6/JAK2/STAT3 signaling. PMID: 29393444
  23. MiR-375 inhibits fetal ASM cell proliferation and migration by targeting the JAK2/STAT3 signaling. PMID: 29245068
  24. Data show that HIT is more frequent during heparin treatment in patients with ET carrying the V617F mutation compared to patients without mutations. PMID: 29022213
  25. Overexpression of ALK4 suppressed glioma cell proliferation, migration, and invasion through the inactivation of the JAK/STAT3 signaling pathway. PMID: 29278854
  26. This study describes a subset of non-small-cell lung cancer patients who had JAK2 amplifications resulting in high expression of PD-L1. PMID: 28795418
  27. High JAK2 expression is associated with hepatocellular carcinoma. PMID: 28677802
  28. JAK2 haplotype 46/1 and JAK2 V617F allele burden in MPN. PMID: 29134760
  29. Low JAK2 expression is associated with gastric cancer. PMID: 28656307
  30. Researchers discovered that tyrosine 78 of Atoh1 is phosphorylated by a Jak2-mediated pathway only in tumor-initiating cells and in human Sonic Hedgehog-type medulloblastoma. PMID: 29168692
  31. This study concludes that the activating JAK2 V617F mutation does not play a decisive role in the pathogenesis of progressive CKD. PMID: 27889755
  32. These findings revealed that B7-H3 affects ovarian cancer progression through the Jak2/Stat3 pathway, indicating that B7-H3 has the potential to be a useful prognostic marker. PMID: 28765941
  33. In 136 patients with myelofibrosis and a median age of 58 years who underwent allogeneic stem cell transplantation (AHSCT) for molecular residual disease, the percentage of molecular clearance on day 100 was higher in CALR-mutated patients (92%) compared to MPL- (75%) and JAKV617F-mutated patients (67%). PMID: 28714945
  34. Mutational subtypes of JAK2 correlate with different clinical features in Japanese patients with myeloproliferative neoplasms. PMID: 29464483
  35. Identification of activating somatic mutations in JAK2 and germline mutations in JAK3 with clinical implications. PMID: 29082853
  36. Screening for the JAK2 V617F mutation in cerebral venous thrombosis patients seems beneficial due to its relatively high prevalence and the risk of thrombosis recurrence. PMID: 28609766
  37. Ascochlorin significantly decreased phosphorylation of JAK2/STAT3, cancer cell migration, and nuclear translocation of STAT3. PMID: 28569433
  38. TLR7, TLR9, and JAK2 genes are potential biomarkers for systemic sclerosis. High TLR7 expression positively correlated with the late form of the disease. Decreased levels of TLR9 and JAK2 mRNA were found in the patient's cohort compared to non-SSc individuals. PMID: 29147913
  39. This study demonstrated that the JAK2V617F mutation was detectable in patients with stroke. PMID: 28625126
  40. Curcumin attenuated neuropathic pain and down-regulated the production of spinal mature IL-1beta by inhibiting the aggregation of NALP1 inflammasome and the activation of the JAK2-STAT3 cascade in astrocytes. PMID: 27381056
  41. High levels of phosphorylated JAK2 and STAT3 are associated with systemic lupus erythematosus. PMID: 28177455
  42. This study shows that Nrf2 activation induces lipocyte phenotype in hepatic stellate cells via enhancing SOCS3-dependent feedback inhibition on the JAK2/STAT3 cascade. PMID: 28601022
  43. Bladder cancer cells may inhibit the maturation and function of dendritic cells involving the Jak2/STAT3 pathway, and there may be different mechanisms by which adriamycin-resistant BCC restrains DC function in antitumor immune response. PMID: 27556503
  44. Multivariate analysis adjusted for age, sex, follow-up period, and hematological parameters confirmed that increased activated B cells were universally present in JAK2-mutated, CALR-mutated, and triple-negative ET patients compared to healthy adults. PMID: 28415571
  45. In multivariable analysis, younger age, platelet count, hemoglobin level, and JAK2 V617F mutation independently predicted the development of acquired von Willebrand syndrome (AVWS) among essential thrombocythemia (ET) patients; whereas only platelet count predicted its development among polycythemia vera (PV) patients. Among ET patients, JAK2 V617F was a main driver for the development of AVWS. PMID: 27919526
  46. CXCR4 induced VEGF production and JAK2/STAT3 activation and enhanced STAT3 binding to the VEGF promoter in gastric cancer cells. PMID: 28544312
  47. These results reveal proteome alterations in MPN granulocytes depending on the phenotype and genotype of patients, highlighting new oncogenic mechanisms associated with JAK2 mutations and overexpression of calreticulin. PMID: 28314843
  48. JAK2 mutation is associated with Essential thrombocythemia. PMID: 28205126
  49. Considering JAK2(V617F)-positive disease, a higher (>50%) JAK2(V617F) burden and histological classification are independent prognostic risk factors for disease progression. PMID: 28509339
  50. Taken together, this study found that silibinin inhibits the Jak2/STAT3/MMP2 signaling pathway and inhibits the proliferation, migration, and invasion of triple-negative breast cancer cells. PMID: 28440514

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Database Links

HGNC: 6192

OMIM: 147796

KEGG: hsa:3717

STRING: 9606.ENSP00000371067

UniGene: Hs.656213

Involvement In Disease
Budd-Chiari syndrome (BDCHS); Polycythemia vera (PV); Thrombocythemia 3 (THCYT3); Myelofibrosis (MYELOF); Leukemia, acute myelogenous (AML)
Protein Families
Protein kinase superfamily, Tyr protein kinase family, JAK subfamily
Subcellular Location
Endomembrane system; Peripheral membrane protein. Cytoplasm. Nucleus.
Tissue Specificity
Ubiquitously expressed throughout most tissues.

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