JAK2 protein – Tyrosine-protein kinase JAK2(JAK2)

General information on JAK2 protein

JAK2 Protein stands for Janus Kinase Protein which is a non-receptor tyrosine kinase. This protein is member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family, the GM-CSF receptor family and the gp130 receptor family and the single chain receptors. JAK2 protein is different from other JAK kinases because it lacks Src homology binding domains (SH2/SH3) and contains up to seven JAK homology domains.

This protein is involved in several cellular activities such as cell growth, cell development, cell differentiation and histone modifications. Jak2 protein is also involved in innate and adaptative immunity response. In the cytoplasm, JAK2 protein, plays a pivotal role in signal transduction via its association with either type I receptors such as prolactin, leptin, erythropoietin and even growth hormone (GHR) or type II receptors including INF-alpha, IFN-beta and INF-gamma. JAK2 protein is also associated with different interleukins which is also linked to signal transduction.

Following the ligand-binding, JAK2 protein gets activated via transphosphorylation of receptor JAK membrane molecules. Once activated, these proteins phosphorylate substrates on tyrosine which provides docking sites to recruit downstream signaling proteins such as STAT family of proteins. The latter are phosphorylated and form a homodimer or a heterodimer and translocate to the nucleus where they activate gene transcription. In addition, JAK2 protein also mediates angiotensin-2-induced ARHGEF1 phosphorylation. JAK2 kinase lays is involved in cell cycle by phosphorylating CDKN1B protein. Other interactions involve its cooperation with TEC vis reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, JAK2 protein is essential for the phosphorylation of ‘Tyr-41’ of histone H3 (H3Y41ph) which promotes exclusion of CBX5 (HP1 alpha) from chromatin. Hence JAk2 protein has been linked to certain malignancies. It has been shown that the absence of JAK2 kinase is lethal in embryonic mice.