Janus kinase 2

JAK22JAKJAK2 kinase
Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase.wikipedia
117 Related Articles

Janus kinase

JAKJAK kinasesJanus Kinases
It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF receptor family (IL-3R, IL-5R and GM-CSF-R), the gp130 receptor family (e.g., IL-6R), and the single chain receptors (e.g. Epo-R, Tpo-R, GH-R, PRL-R). 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).

TEL-JAK2

JAK2 gene fusions with the TEL(ETV6) (TEL-JAK2) and PCM1 genes have been found in patients suffering leukemia, particularly clonal eosinophilia forms of the disease.
TEL-JAK2 is a gene fusion resulting from a chromosomal translocation between chromosomes 9 and 12 observed in human leukemia.

Non-receptor tyrosine kinase

EC 2.7.10.2Ncknon receptor tyrosine kinases
Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase.
In contrast, another mutant of the Jak family Jak2, also lacking the pseudo-kinase domain, was able to mediate growth hormone signaling.

Growth hormone receptor

GHRGH receptorGH receptor antagonist
It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF receptor family (IL-3R, IL-5R and GM-CSF-R), the gp130 receptor family (e.g., IL-6R), and the single chain receptors (e.g. Epo-R, Tpo-R, GH-R, PRL-R).
Growth hormone receptor has been shown to interact with SGTA, PTPN11, Janus kinase 2, Suppressor of cytokine signaling 1 and CISH.

SH2 domain

SH2ShcSrc homology 2
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).

Myelofibrosis

primary myelofibrosismyeloid metaplasiaagnogenic myeloid metaplasia
Mutations in JAK2 have been implicated in polycythemia vera, essential thrombocythemia, and myelofibrosis as well as other myeloproliferative disorders.
There is an association between mutations to the JAK2, CALR, or MPL gene and myelofibrosis.

Clonal hypereosinophilia

clonal eosinophiliaPDGFRAETV6-ACSL6
JAK2 gene fusions with the TEL(ETV6) (TEL-JAK2) and PCM1 genes have been found in patients suffering leukemia, particularly clonal eosinophilia forms of the disease.
Chromosome translocations between the PDGFRA gene and either the FIP1L1, KIF5B, CDK5RAP2, STRN, ETV6, FOXP1, TNKS2, BCR or JAK2 gene create a fusion gene which codes for a chimeric protein consisting of the tyrosine kinase portion of PDGFRA and a portion of these other genes.

Thrombopoietin receptor

MPLc-mplMyeloproliferative leukemia virus oncogene
It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF receptor family (IL-3R, IL-5R and GM-CSF-R), the gp130 receptor family (e.g., IL-6R), and the single chain receptors (e.g. Epo-R, Tpo-R, GH-R, PRL-R).

Interleukin-5 receptor

IL-5 receptorIL-5RIL5R
It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF receptor family (IL-3R, IL-5R and GM-CSF-R), the gp130 receptor family (e.g., IL-6R), and the single chain receptors (e.g. Epo-R, Tpo-R, GH-R, PRL-R).
As with the IL-5Rα subunit, the β subunit’s cytoplasmic domain is constitutively associated with JAK2, as well as LYN, another tyrosine kinase, which are both essential for IL-5 signal transduction.

Essential thrombocythemia

essential thrombocytosisessential thrombocythaemiaEssential thrombocytemia
Mutations in JAK2 have been implicated in polycythemia vera, essential thrombocythemia, and myelofibrosis as well as other myeloproliferative disorders.
A mutation in the JAK2 kinase (V617F) is present in 40–50% of cases and is diagnostic if present.

Polycythemia vera

polycythaemia verapolycythaemia rubra veraErythremia
Mutations in JAK2 have been implicated in polycythemia vera, essential thrombocythemia, and myelofibrosis as well as other myeloproliferative disorders.
Instead, PCV cells often carry activating mutation in the tyrosine kinase (JAK2) gene, which acts in signaling pathways of the EPO-receptor, making those cells proliferate independent from EPO.

Myeloproliferative neoplasm

myeloproliferative diseasemyeloproliferative disordermyeloproliferative disorders
Mutations in JAK2 have been implicated in polycythemia vera, essential thrombocythemia, and myelofibrosis as well as other myeloproliferative disorders.
Most Philadelphia chromosome negative cases have an activating JAK2 or MPL mutation.

Erythropoietin receptor

EPOREpo-Rerythropoietin (EPO) receptor
It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF receptor family (IL-3R, IL-5R and GM-CSF-R), the gp130 receptor family (e.g., IL-6R), and the single chain receptors (e.g. Epo-R, Tpo-R, GH-R, PRL-R).
These conformational changes result in the autophosphorylation of Jak2 kinases that are pre-associated with the receptor (i.e., EpoR does not possess intrinsic kinase activity and depends on Jak2 activity).

Erythropoietin

EPOrecombinant EPOerythropoetin
This mutation (V617F), a change of valine to phenylalanine at the 617 position, appears to render hematopoietic cells more sensitive to growth factors such as erythropoietin and thrombopoietin, because the receptors for these growth factors require JAK2 for signal transduction.
EPO binds to the erythropoietin receptor on the red cell progenitor surface and activates a JAK2 signalling cascade.

Prolactin

PRLlactationprolactin secretion
Prolactin signals through JAK2 are dependent on STAT5, and on the RUSH transcription factors.
This results in the activation of Janus kinase 2, a tyrosine kinase that initiates the JAK-STAT pathway.

Janus kinase inhibitor

inhibitorinhibitor of JAK1inhibitor of janus kinase
Janus kinase inhibitors, also known as JAK inhibitors or jakinibs, are a type of medication that functions by inhibiting the activity of one or more of the Janus kinase family of enzymes (JAK1, JAK2, JAK3, TYK2), thereby interfering with the JAK-STAT signaling pathway.

STAT5

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

Ruxolitinib

Jakafi
Ruxolitinib is a janus kinase inhibitor (JAK inhibitor) with selectivity for subtypes JAK1 and JAK2.