JAK2: a non-receptor tyrosine-kinase involved in a specific subset of cytokine receptor signaling pathways, including IL-3, -5 and GM-CSF. Interacts with IL23R, SKB1 and STAM2. It has been found to be constitutively associated with the prolactin receptor and is required for responses to gamma interferon. Mice that do not express an active protein for this gene exhibit embryonic lethality associated with the absence of definitive erythropoiesis. Fusion of Jak2 to TEL1 (ETV6) by t(9;12)(p24;p13) causes myeloproliferative disease in humans and mouse models. The Jak inhibitor AG490 inhibits constitutive Jak2 phosphorylation and causes apoptosis in cells from breast cancer and relapsing acute lymphoblastic leukemia. A single activating mutation is associated with several hematological malignancies. Inhibitor: AG490.
Protein type: EC 2.7.10.2; JakA family; Kinase, protein; Oncoprotein; Protein kinase, TK; Protein kinase, tyrosine (non-receptor); TK group
Chromosomal Location of Human Ortholog: 9p24.1
Cellular Component: caveola; cytoplasm; cytoskeleton; cytosol; extrinsic component of cytoplasmic side of plasma membrane; focal adhesion; membrane raft; nuclear matrix; nucleoplasm; nucleus; plasma membrane
Molecular Function: acetylcholine receptor binding; ATP binding; growth hormone receptor binding; heme binding; histone binding; identical protein binding; insulin receptor substrate binding; interleukin-12 receptor binding; metal ion binding; non-membrane spanning protein tyrosine kinase activity; peptide hormone receptor binding; phosphoinositide 3-kinase binding; protein binding; protein C-terminus binding; protein kinase activity; protein kinase binding; protein tyrosine kinase activity; Ras guanyl-nucleotide exchange factor activity; receptor binding; SH2 domain binding; type 1 angiotensin receptor binding
Biological Process: actin filament polymerization; activation of cysteine-type endopeptidase activity involved in apoptotic process; activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; activation of JAK protein; activation of MAPKK activity; adaptive immune response; apoptosis; axon regeneration; blood coagulation; cell differentiation; cell migration; cell motility; cytokine-mediated signaling pathway; elevation of cytosolic calcium ion concentration; enzyme linked receptor protein signaling pathway; erythrocyte differentiation; G-protein coupled receptor signaling pathway; induction of apoptosis by oxidative stress; innate immune response; JAK-STAT cascade; MAPK cascade; mesoderm development; mineralocorticoid receptor signaling pathway; negative regulation of cardiac muscle cell apoptotic process; negative regulation of cell proliferation; negative regulation of cell-cell adhesion; negative regulation of DNA binding; negative regulation of heart contraction; negative regulation of neuron apoptosis; peptidyl-tyrosine autophosphorylation; peptidyl-tyrosine phosphorylation; platelet-derived growth factor receptor signaling pathway; positive regulation of cell activation; positive regulation of cell differentiation; positive regulation of cell migration; positive regulation of cell-substrate adhesion; positive regulation of DNA binding; positive regulation of epithelial cell apoptotic process; positive regulation of growth factor dependent skeletal muscle satellite cell proliferation; positive regulation of inflammatory response; positive regulation of insulin secretion; positive regulation of interleukin-1 beta production; positive regulation of nitric oxide biosynthetic process; positive regulation of nitric-oxide synthase biosynthetic process; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of phosphoinositide 3-kinase cascade; positive regulation of phosphoprotein phosphatase activity; positive regulation of protein import into nucleus, translocation; positive regulation of transcription factor activity; positive regulation of tumor necrosis factor production; positive regulation of tyrosine phosphorylation of STAT protein; positive regulation of vascular smooth muscle cell proliferation; protein amino acid phosphorylation; protein autophosphorylation; regulation of apoptosis; regulation of cell proliferation; regulation of inflammatory response; response to antibiotic; response to hydroperoxide; response to lipopolysaccharide; response to tumor necrosis factor; signal transduction; STAT protein import into nucleus; tumor necrosis factor-mediated signaling pathway; tyrosine phosphorylation of STAT protein
Disease: Budd-chiari Syndrome; Erythrocytosis, Familial, 1; Myelofibrosis; Polycythemia Vera; Thrombocythemia 3
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