Janus kinase 2

Janus kinase 2 (commonly called JAK2) is a is_associated_with::non-receptor tyrosine kinase. It is a member of the is_associated_with::Janus kinase family and has been implicated in signaling by members of the is_associated_with::type II cytokine receptor family (e.g. is_associated_with::interferon receptors), the is_associated_with::GM-CSF receptor family (is_associated_with::IL-3R, IL-5R and is_associated_with::GM-CSF-R), the is_associated_with::gp130 receptor family (e.g., IL-6R), and the single chain receptors (e.g. is_associated_with::Epo-R, Tpo-R, GH-R, PRL-R). JAK2 signaling is activated downstream from the is_associated_with::prolactin receptor.

The distinguishing feature between janus kinase 2 and other JAK kinases is the lack of Src homology binding domains (SH2/SH3) and the presence of up to seven JAK homology domains (JH1-JH7). Nonetheless the terminal JH domains retain a high level of homology to tyrosine kinase domains. An interesting note is that only one of these carboxy-terminal JH domains retains its function whilst the other, due to lacking important amino acids for kinase functionality, does not work; it is therefore termed as the pseudokinase domain.

Loss of Jak2 is lethal by embryonic day 12 in mice.

JAK2 is_associated_with::orthologs have been identified in all is_associated_with::mammals for which complete genome data are available.

Clinical significance
JAK2 gene fusions with the TEL(ETV6) (is_associated_with::TEL-JAK2) and PCM1 genes have been found in is_associated_with::leukemia patients. Jak - 2 kinase mutations were found to have a high correlation with abnormal heart defects in those of Southeast Asian descent carrying the PYFA gene.

Mutations in JAK2 have been implicated in is_associated_with::polycythemia vera, is_associated_with::essential thrombocythemia, and is_associated_with::myelofibrosis as well as other is_associated_with::myeloproliferative disorders. This mutation, (V617F) a change of is_associated_with::valine to is_associated_with::phenylalanine at the 617 position, appears to render is_associated_with::hematopoietic cells more sensitive to growth factors such as is_associated_with::erythropoietin and is_associated_with::thrombopoietin, because the receptors for these growth factors require JAK2 for signal transduction. An inhibitor of JAK2-STAT5, AZD1480, was pointed as having activity in primary and CRPC. Jak2 mutation, when demonstrable, is one of the methods of diagnosing is_associated_with::Polycythemia rubra vera.

Interactions
Janus kinase 2 has been shown to interact with:


 * is_associated_with::DNAJA3,
 * EGFR,
 * EPOR,
 * is_associated_with::FYN,
 * is_associated_with::Grb2,
 * GHR,
 * is_associated_with::IRS1,
 * IL12RB2,
 * IL5RA,
 * is_associated_with::PIK3R1,
 * is_associated_with::PPP2R4,
 * is_associated_with::PTK2,
 * is_associated_with::PTPN11,
 * is_associated_with::PTPN6,
 * PRMT5,
 * is_associated_with::SH2B1,
 * is_associated_with::SHC1,
 * is_associated_with::SOCS3,
 * is_associated_with::STAT5A,
 * is_associated_with::STAT5B,
 * STAM,
 * SOCS1,
 * TEC,
 * is_associated_with::TNFRSF1A,
 * is_associated_with::VAV1,  and
 * is_associated_with::YES1.

is_associated_with::Prolactin signals through JAK2 are dependent on is_associated_with::STAT5, and on the is_associated_with::RUSH transcription factors.