Janus kinase

Source: Wikipedia, the free encyclopedia.

Janus kinase (JAK) is a family of intracellular,

Janus
, because the JAKs possess two near-identical phosphate-transferring domains. One domain exhibits the kinase activity, while the other negatively regulates the kinase activity of the first.

Family

Overview of signal transduction pathways involved in apoptosis

The four JAK family members are:

Transgenic mice that do not express JAK1 have defective responses to some cytokines, such as

type I interferon signalling. Mice that do not express TYK2 have defective natural killer cell function.[3]

Functions

The JAK-STAT system consists of three main components: (1) a receptor (green), which penetrates the cell membrane; (2) Janus kinase (JAK) (yellow), which is bound to the receptor, and; (3) Signal Transducer and Activator of Transcription (STAT) (blue), which carries the signal into the nucleus and DNA. The red dots are phosphates. After the cytokine binds to the receptor, JAK adds a phosphate to (phosphorylates) the receptor. This attracts the STAT proteins, which are also phosphorylated and bind to each other, forming a pair (dimer). The dimer moves into the nucleus, binds to the DNA, and causes transcription of genes. Enzymes that add phosphate groups are called protein kinases.

Since members of the

phosphorylate and activate downstream proteins involved in their signal transduction pathways. The receptors
exist as paired polypeptides, thus exhibiting two intracellular signal-transducing domains.

JAKs associate with a

transcription of selected genes
.

Some examples of the molecules that use the JAK/STAT signaling pathway are

cytokines. Janus Kinases have also been reported to have a role in the maintenance of X chromosome inactivation.[5]

Clinical significance

myelofibrosis and vitiligo.[6][7] Examples are tofacitinib, baricitinib, upadacitinib and filgotinib.[8]

In 2014 researchers discovered that oral JAK inhibitors, when administered orally, could restore hair growth in some subjects and that applied to the skin, effectively promoted hair growth.[9]

Structure

Domain structure of Janus kinases, JH = JAK homology domain

JAKs range from 120-140

focal adhesion kinase (FAK) family and is involved in association of JAKs with cytokine receptors and/or other kinases.[4]

References

  1. PMID 2466296
    .
  2. PMID 9590172
    .
  3. PMID 15578097
    .
  4. ^
    PMID 12039028
    .
  5. ISSN 1866-1947
    .
  6. ^ Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy: D. Golan et al. LWW. 2007
  7. PMID 26107994
    .
  8. ^ "Search of: GLPG0634 - List Results - ClinicalTrials.gov". clinicaltrials.gov.
  9. ^ "FDA-approved drugs show promise for rapid and robust hair regrowth". www.gizmag.com. 26 October 2015. Retrieved 2015-10-29.
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