Janus kinase

JAKJAK kinasesJanus KinasesJAK (Janus kinase) receptorJak familyJAK kinaseJAK tyrosine kinaseJAK/StatJAK1JAK3
Janus kinase (JAK) is a family of intracellular, nonreceptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway.wikipedia
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JAK-STAT signaling pathway

JAK-STAT pathwayJAK-STATJAK/STAT
Janus kinase (JAK) is a family of intracellular, nonreceptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway.
There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs), and receptors (which bind the chemical signals).

Tyrosine kinase

tyrosine kinasesprotein-tyrosine kinaseprotein tyrosine kinase
Janus kinase (JAK) is a family of intracellular, nonreceptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. Since members of the type I and type II cytokine receptor families possess no catalytic kinase activity, they rely on the JAK family of tyrosine kinases to phosphorylate and activate downstream proteins involved in their signal transduction pathways.
The results of some newer research have also indicated that the aforementioned cytokine receptors function with members of the JAK tyrosine kinase family.

Janus kinase 2

JAK22JAK
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).

Janus kinase 3

JAK3
Janus kinase 3 is a tyrosine kinase that belongs to the janus family of kinases.

Tyrosine kinase 2

TYK2TYK
Tyk2 was the first member of the JAK family that was described (the other members are JAK1, JAK2, and JAK3).

Kinase

kinaseskinase domainprotein kinase C
Since members of the type I and type II cytokine receptor families possess no catalytic kinase activity, they rely on the JAK family of tyrosine kinases to phosphorylate and activate downstream proteins involved in their signal transduction pathways.
During this time, the MAPK/ERK pathway, the JAK kinases (a family of protein tyrosine kinases), and the PIP3-dependent kinase cascade were discovered.

STAT protein

STATSTAT transcription factorsstat1 transcription factor
The JAK autophosphorylation induces a conformational change within itself, enabling it to transduce the intracellular signal by further phosphorylating and activating transcription factors called STATs (Signal Transducer and Activator of Transcription, or Signal Transduction And Transcription).
They are primarily activated by membrane receptor-associated Janus kinases (JAK).

Janus kinase inhibitor

inhibitorinhibitor of JAK1inhibitor of janus kinase
JAK inhibitors are under development for the treatment of psoriasis, rheumatoid arthritis, polycythemia vera, alopecia, essential thrombocythemia, ulcerative colitis, myeloid metaplasia with myelofibrosis and vitiligo.
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.

Type II cytokine receptor

cytokine receptor class II familyInterferon receptorsType 2
Since members of the type I and type II cytokine receptor families possess no catalytic kinase activity, they rely on the JAK family of tyrosine kinases to phosphorylate and activate downstream proteins involved in their signal transduction pathways.
The intracellular domain of type II cytokine receptors is typically associated with a tyrosine kinase belonging to the Janus kinase (JAK) family.

Tofacitinib

tasocitinibTofacitinib citrateXeljanz
Examples are tofacitinib and filgotinib (GLPG0634), the latter is currently under development by the Belgian firm Galapagos.
It is in the janus kinase (JAK) inhibitor class, discovered and developed by the National Institutes of Health and Pfizer.

Polycythemia vera

polycythaemia verapolycythaemia rubra veraErythremia
JAK inhibitors are under development for the treatment of psoriasis, rheumatoid arthritis, polycythemia vera, alopecia, essential thrombocythemia, ulcerative colitis, myeloid metaplasia with myelofibrosis and vitiligo.
JAK2 is a member of the Janus kinase family and makes the erythroid precursors hypersensitive to erythropoietin (EPO).

Polymerase chain reaction

PCRPCR amplificationpolymerase chain reaction (PCR)
They were initially named "just another kinase" 1 and 2 (since they were just two of many discoveries in a PCR-based screen of kinases), but were ultimately published as "Janus kinase".

Roman mythology

RomanRoman godRoman goddess
The name is taken from the two-faced Roman god of beginnings, endings and duality, Janus, because the JAKs possess two near-identical phosphate-transferring domains.

Janus

IanusDianusRoman god
The name is taken from the two-faced Roman god of beginnings, endings and duality, Janus, because the JAKs possess two near-identical phosphate-transferring domains.

Interferon gamma

IFN-γinterferon-gammaIFNγ
Transgenic mice that do not express JAK1 have defective responses to some cytokines, such as interferon-gamma.

Natural killer cell

NK cellsnatural killer cellsNK cell
Mice that do not express TYK2 have defective natural killer cell function.

Type I cytokine receptor

type IClass I Haematopoeitin receptorscytokine type I receptor
Since members of the type I and type II cytokine receptor families possess no catalytic kinase activity, they rely on the JAK family of tyrosine kinases to phosphorylate and activate downstream proteins involved in their signal transduction pathways.

Phosphorylation

phosphorylatedphosphorylatephosphorylates
Since members of the type I and type II cytokine receptor families possess no catalytic kinase activity, they rely on the JAK family of tyrosine kinases to phosphorylate and activate downstream proteins involved in their signal transduction pathways. After the receptor associates with its respective cytokine/ligand, it goes through a conformational change, bringing the two JAKs close enough to phosphorylate each other.

Signal transduction

signaling pathwayssignaling cascadesignal transduction pathways
Since members of the type I and type II cytokine receptor families possess no catalytic kinase activity, they rely on the JAK family of tyrosine kinases to phosphorylate and activate downstream proteins involved in their signal transduction pathways.

Receptor (biochemistry)

receptorreceptorscellular receptors
The receptors exist as paired polypeptides, thus exhibiting two intracellular signal-transducing domains.

Proline

ProL-proline L -proline
JAKs associate with a proline-rich region in each intracellular domain that is adjacent to the cell membrane and called a box1/box2 region.

Intracellular

intracellular spaceinside cellswithin the cell
JAKs associate with a proline-rich region in each intracellular domain that is adjacent to the cell membrane and called a box1/box2 region.

Cell membrane

plasma membranemembranecell membranes
JAKs associate with a proline-rich region in each intracellular domain that is adjacent to the cell membrane and called a box1/box2 region.

Ligand

ligandsligand exchangebidentate ligand
After the receptor associates with its respective cytokine/ligand, it goes through a conformational change, bringing the two JAKs close enough to phosphorylate each other.