JAK2

Description

The JAK2 (Janus kinase 2) is a protein-coding gene located on chromosome 9.

The JAK2 gene provides instructions for making a protein that promotes the growth and division (proliferation) of cells. This protein is part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell's nucleus. The JAK2 protein is especially important for controlling the production of blood cells from hematopoietic stem cells. These stem cells are located within the bone marrow and have the potential to develop into red blood cells, white blood cells, and platelets.

JAK2 is a non-receptor tyrosine kinase involved in various cellular processes like growth, development, differentiation, and histone modifications. It plays a crucial role in both innate and adaptive immunity. In the cytoplasm, JAK2 acts as a signaling mediator by associating with type I receptors (growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO)) and type II receptors (IFN-alpha, IFN-beta, IFN-gamma, and multiple interleukins). Following ligand binding to cell surface receptors, JAK2 phosphorylates tyrosine residues on the receptor's cytoplasmic tails, creating docking sites for STATs proteins. Subsequently, it phosphorylates the STATs proteins recruited to the receptor. Phosphorylated STATs form dimers (homodimers or heterodimers) and translocate to the nucleus to activate gene transcription. For instance, during erythropoiesis, erythropoietin (EPO) stimulation leads to JAK2 autophosphorylation, activation, and association with the erythropoietin receptor (EPOR), which gets phosphorylated in its cytoplasmic domain. STAT5 (STAT5A or STAT5B) is then recruited, phosphorylated, and activated by JAK2. Activated and dimerized STAT5 translocates into the nucleus and promotes transcription of genes involved in erythropoiesis regulation. JAK2 is part of a signaling cascade activated by increased cellular retinol, leading to STAT5 (STAT5A or STAT5B) activation. Additionally, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation, plays a role in the cell cycle by phosphorylating CDKN1B, and cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven FOS transcription activation. In the nucleus, JAK2 contributes to chromatin regulation by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a tag promoting CBX5 (HP1 alpha) exclusion from chromatin.

JAK2 is also known as JTK10.

Associated Diseases

Whole Exome Sequencing

WES Whole Exome Sequencing

Clinical Exome Sequencing