Summary

Name JAK2
Full Name Tyrosine-protein kinase JAK2
Synonyms Janus kinase 2, JAK-2
Primary ID O60674
Links - -
Type protein
Relations 124
Pathways Macrophage polarization, Acute Myeloid Leukemia
Inhibitors AZ 960; Tg-101348; Ruxolitinib; Tyrphostin B42; TG101209; AT9283; AZD1480; Erlotinib hydrochloride; Cyt387; LY2784544; NVP-BSK805 dihydrochloride
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 (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins (PubMed:7615558). 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: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. 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).

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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates img/direct_inhibition.png phosphorylation JAK2
Publications: 1 Organism: Chlorocebus Aethiops
Pathways:Acute Myeloid Leukemia
+ down-regulates img/direct_inhibition.png phosphorylation JAK2 0.15
Publications: 1 Organism: Chlorocebus Aethiops
+ down-regulates activity img/direct_inhibition.png phosphorylation JAK2
Publications: 3 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, Macrophage polarization
+ down-regulates img/direct_inhibition.png phosphorylation JAK2 0.15
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation JAK2
Publications: 1 Organism: In Vitro
Pathways:Acute Myeloid Leukemia, Macrophage polarization
+ up-regulates activity img/direct-activation.png phosphorylation JAK2 0.24
Publications: 2 Organism: In Vitro
Pathways:Acute Myeloid Leukemia
+ down-regulates img/direct_inhibition.png dephosphorylation JAK2 0.08
Publications: 3 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation JAK2
Publications: 6 Organism: In Vitro, Chlorocebus Aethiops, Homo Sapiens
Pathways:Acute Myeloid Leukemia, Macrophage polarization
+ up-regulates activity img/direct-activation.png phosphorylation JAK2 0.26
Publications: 2 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png dephosphorylation JAK2
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ down-regulates activity img/direct_inhibition.png dephosphorylation JAK2
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation JAK2 0.08
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation JAK2
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation JAK2
Publications: 3 Organism: Mus Musculus
Pathways:Acute Myeloid Leukemia
+ up-regulates activity img/direct-activation.png phosphorylation EGFR 0.11
Publications: 1 Organism: Chlorocebus Aethiops
+ up-regulates activity img/direct-activation.png phosphorylation CCR2
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation CTLA4 0.09
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation JAK2
Publications: 3 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, Macrophage polarization
+ up-regulates activity img/direct-activation.png phosphorylation GTF2I 0.16
Publications: 1 Organism: Mus Musculus
+ up-regulates activity img/direct-activation.png phosphorylation STAP2 0.06
Publications: 2
+ down-regulates img/direct_inhibition.png phosphorylation PRMT5 0.06
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation PTPN11 0.30
Publications: 2 Organism: Chlorocebus Aethiops
Pathways:Acute Myeloid Leukemia
+ down-regulates img/direct_inhibition.png phosphorylation JAK2
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, Macrophage polarization
+ up-regulates activity img/direct-activation.png phosphorylation RAF1 0.15
Publications: 2 Organism: Mus Musculus
+ up-regulates activity img/direct-activation.png phosphorylation EPOR 0.54
Publications: 8
+ down-regulates img/direct_inhibition.png phosphorylation EZH2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation GAB2 0.15
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation STAT4 0.16
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation STAT5A
Publications: 5 Organism: Homo Sapiens,
Pathways:Acute Myeloid Leukemia
+ up-regulates img/direct-activation.png phosphorylation STAT1 0.69
Publications: 2 Organism: Homo Sapiens, Neorhizobium Galegae
+ up-regulates activity img/direct-activation.png phosphorylation STAT3 0.82
Publications: 5 Organism: Homo Sapiens, Cricetulus Griseus
Pathways:Acute Myeloid Leukemia, Macrophage polarization
+ down-regulates img/direct_inhibition.png phosphorylation MAP3K5 0.12
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ARHGEF1 0.08
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle, Smooth Muscle
+ up-regulates activity img/direct-activation.png phosphorylation JAK2
Publications: 1 Organism: Mus Musculus
Pathways:Acute Myeloid Leukemia
+ down-regulates img/direct_inhibition.png chemical inhibition JAK2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding JAK2 0.20
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation IFNGR1 0.20
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition JAK2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding JAK2 0.26
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png dephosphorylation JAK2
Publications: 1
Pathways:Acute Myeloid Leukemia
+ up-regulates activity img/direct-activation.png unknown APOA1 0.05
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png unknown JAK2 0.05
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png binding MYC 0.09
Publications: 1 Organism: Mus Musculus
Pathways:Acute Myeloid Leukemia
+ up-regulates quantity by expression img/indirect-activation.png transcriptional activation MYC 0.09
Publications: 1 Organism: Mus Musculus
Pathways:Acute Myeloid Leukemia
+ up-regulates activity img/direct-activation.png binding JAK2 0.24
Publications: 1
+ down-regulates img/direct_inhibition.png chemical inhibition JAK2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png unknown JAK2 0.19
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ITGB2 0.09
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ITGAL 0.06
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding JAK2 0.04
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding JAK2 0.24
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ up-regulates img/direct-activation.png phosphorylation STAT1A/STAT3/STAT5A/STAT5B
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png unknown JAK2 0.13
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation STAM 0.10
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation JAK2
Publications: 1
+ down-regulates img/direct_inhibition.png binding JAK2
Publications: 1
+ up-regulates activity img/direct-activation.png binding JAK2 0.13
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png unknown JAK2
Publications: 1 Organism: Homo Sapiens
Tissue: Skeletal Muscle
+ up-regulates activity img/direct-activation.png binding IFNGR2 0.26
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation STAT5A
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ down-regulates activity img/direct_inhibition.png unknown, chemical inhibition JAK2
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding JAK2 0.20
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding JAK2
Publications: 1 Organism: Homo Sapiens
Pathways:Macrophage polarization
+ down-regulates img/direct_inhibition.png chemical inhibition JAK2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition JAK2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png unknown JAK2 0.11
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png binding JAK2 0.29
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation IFNGR2/INFGR1
Publications: 1 Organism: Homo Sapiens
Pathways:Macrophage polarization
+ down-regulates img/direct_inhibition.png chemical inhibition JAK2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding JAK2 0.08
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination JAK2 0.55
Publications: 1 Organism: Homo Sapiens
Pathways:Macrophage polarization
+ up-regulates img/direct-activation.png binding JAK2 0.15
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition JAK2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition JAK2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png dephosphorylation JAK2 0.06
Publications: 1 Organism: Homo Sapiens
Tissue: Breast
+ up-regulates img/direct-activation.png phosphorylation STAT5B 0.51
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation STAT6 0.24
Publications: 1 Organism: Homo Sapiens
Pathways:Macrophage polarization
+ up-regulates activity img/direct-activation.png phosphorylation JAK2
Publications: 1 Organism: Homo Sapiens
Pathways:Macrophage polarization
+ up-regulates activity img/direct-activation.png phosphorylation STAT6
Publications: 1 Organism: Homo Sapiens
Pathways:Macrophage polarization
+ down-regulates img/direct_inhibition.png chemical inhibition JAK2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition JAK2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation JAK2
Publications: 1 Organism: Homo Sapiens
Pathways:Macrophage polarization
+ down-regulates activity img/direct_inhibition.png dephosphorylation JAK2
Publications: 1 Organism: Chlorocebus Aethiops
+ down-regulates img/direct_inhibition.png binding JAK2 0.06
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CSF2RA 0.13
Publications: 1 Organism: Homo Sapiens