JAK2 phospho Y1007 + Y1008
GeneName
JAK2
Summary
JAK2, also known as Janus kinase 2, is a 131 kDa non-membrane spanning protein tyrosine kinase that is primarily expressed in the cytoplasm and nucleus of various cell types, including hematopoietic cells. It plays a pivotal role in the JAK-STAT signalling pathway, which is crucial for mediating cellular responses to a variety of cytokines and growth factors. JAK2 is involved in processes such as erythrocyte differentiation, immune response, and cell adhesion, and it interacts with multiple receptors, including those for interleukins and growth hormones. The protein is also associated with various cellular components, including caveolae, endosomes, and the cytoskeleton, reflecting its diverse functional roles in signal transduction and cellular regulation.
Importance
JAK2 is relevant to: - Myeloproliferative neoplasms, particularly in the context of mutations that lead to constitutive activation and disease progression - Immune system regulation, as it mediates signalling for several cytokines involved in inflammation and immune responses - Cancer research, due to its role in cell proliferation and survival pathways that can be hijacked in malignancies - Therapeutic targeting, as inhibitors of JAK2 are being explored for the treatment of various hematological disorders and autoimmune diseases.
Top Products
For researchers investigating JAK2, we highly recommend the top-selling recombinant antibody, Anti-JAK2 antibody [EPR108(2)] (ab108596). This antibody has been validated in knockout models, ensuring reliable performance in various applications, including Western blotting (WB), immunocytochemistry (ICC), and immunoprecipitation (IP). With 256 citations, it is well-regarded in the research community, making it a trusted choice for those studying JAK2. Its recombinant nature also guarantees batch-to-batch consistency, which is essential for reproducible results in your experiments. The Recombinant human JAK2 protein (Active) ELISA Kit (ab268691) is an excellent option for researchers looking to study JAK2 in their experiments.
Abcam Product Citation Summary
The data indicates that JAK2 is frequently studied in various human and mouse tissues, particularly in the context of cancer and signalling pathways. The use of the Abcam antibody ab108596 in Western blotting highlights its role in understanding JAK2's involvement in processes such as apoptosis, inflammation, and the modulation of signalling pathways like IL-6/STAT3 and JAK2/STAT3. The studies span a range of conditions, including hematopoietic injury, cancer, and metabolic effects, suggesting JAK2's significance in both normal physiology and disease states.
Abcam Product Citation Table
Domain
Possesses 2 protein kinase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for protein kinase 1 (By similarity).
Function
Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin receptor (MPL/TPOR); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins (PubMed:15690087, PubMed:7615558, PubMed:9657743, PubMed:15899890). Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:15690087, PubMed:9618263). Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain (PubMed:9657743). Then, 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. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, 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 (PubMed:19783980). Up-regulates the potassium voltage-gated channel activity of KCNA3 (PubMed:25644777).
Involvement in disease
Chromosomal aberrations involving JAK2 are found in both chronic and acute forms of eosinophilic, lymphoblastic and myeloid leukemia. Translocation t(8;9)(p22;p24) with PCM1 links the protein kinase domain of JAK2 to the major portion of PCM1. Translocation t(9;12)(p24;p13) with ETV6.
Budd-Chiari syndrome
BDCHS
A syndrome caused by obstruction of hepatic venous outflow involving either the hepatic veins or the terminal segment of the inferior vena cava. Obstructions are generally caused by thrombosis and lead to hepatic congestion and ischemic necrosis. Clinical manifestations observed in the majority of patients include hepatomegaly, right upper quadrant pain and abdominal ascites. Budd-Chiari syndrome is associated with a combination of disease states including primary myeloproliferative syndromes and thrombophilia due to factor V Leiden, protein C deficiency and antithrombin III deficiency. Budd-Chiari syndrome is a rare but typical complication in patients with polycythemia vera.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Polycythemia vera
PV
A myeloproliferative disorder characterized by abnormal proliferation of all hematopoietic bone marrow elements, erythroid hyperplasia, an absolute increase in total blood volume, but also by myeloid leukocytosis, thrombocytosis and splenomegaly.
None
The disease is caused by variants affecting the gene represented in this entry.
Thrombocythemia 3
THCYT3
A myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes.
None
The disease may be caused by variants affecting the gene represented in this entry.
Myelofibrosis
MYELOF
A disorder characterized by replacement of the bone marrow by fibrous tissue, occurring in association with a myeloproliferative disorder. Clinical manifestations may include anemia, pallor, splenomegaly, hypermetabolic state, petechiae, ecchymosis, bleeding, lymphadenopathy, hepatomegaly, portal hypertension.
None
The disease is caused by variants affecting the gene represented in this entry.
Leukemia, acute myelogenous
AML
A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Autophosphorylated, leading to regulate its activity. Leptin promotes phosphorylation on tyrosine residues, including phosphorylation on Tyr-813 (By similarity). Autophosphorylation on Tyr-119 in response to EPO down-regulates its kinase activity (By similarity). Autophosphorylation on Tyr-868, Tyr-966 and Tyr-972 in response to growth hormone (GH) are required for maximal kinase activity (By similarity). Also phosphorylated by TEC (By similarity). Phosphorylated on tyrosine residues in response to interferon gamma signaling (PubMed:7615558, PubMed:7673114). Phosphorylated on tyrosine residues in response to a signaling cascade that is activated by increased cellular retinol (PubMed:21368206).
Undergoes Notch-induced ubiquitination and subsequent proteasomal degradation which is mediated by ASB1 or ASB2, the substrate-recognition components of probable ECS E3 ubiquitin-protein ligase complexes.
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.
Tissue Specificity
Ubiquitously expressed throughout most tissues.
Cellular localization
- Endomembrane system
- Peripheral membrane protein
- Cytoplasm
- Nucleus
Alternative names
Tyrosine-protein kinase JAK2, Janus kinase 2, JAK-2, JAK2
Database links
Other research areas
- Epigenetics
- Immuno-oncology
- Oncology