Jak

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 05.03.2021

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Synonym(s)

Januskinases; Janus Kinases

Definition
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Acronym for "Janus kinases - actually for "Just Another Kinase". Janus kinases are cytoplasmically localized tyrosine kinases that occur, for example, in the chains of action of cytokine receptors. Janus kinases (JAKs) are intracellular enzymes that transduce cytokine and growth factor signals involved in a variety of cellular processes, including inflammatory responses, hematopoiesis, and immune surveillance.

General information
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In general, extracellular signal peptides such as growth factors on target cells are bound by specific transmembrane receptors with their own tyrosine kinase activity. In contrast, most cytokine receptors of the JAK-STAT pathway do not possess an independent tyrosine kinase activity. This tyrosine kinase activity is provided by cytoplasmic proteins of the so-called Janus kinase family.

The JAK enzyme family comprises four members:

JAK1

JAK2

JAK3 and

TYK2 , which phosphorylate and thereby activate paired signal transducers and activators of transcription (STATs). This phosphorylation in turn modulates gene expression and cell function. JAK1 is important for inflammatory cytokine signaling pathways, while JAK2 is important for erythrocyte maturation and JAK3 signaling plays a role in immune surveillance and lymphocyte function.

Inhibition of JAK 2 may play a role in the therapy of psoriasis vulgaris. Janus kinase inhibitors have been successfully used in alopecia areata (experimental).

The recently successful specific inhibition of JAK3 promises selective immunosuppression, which could have clinical relevance for rheumatoid arthritis (Forster M 2016).

JAK2 mutations (JAK2V617 mutation) are highly associated with aquagenic pruritus associated with polycythemia vera.

Note(s)
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It was named after the Roman god Ianus.

A few years ago, the first JAK kinase inhibitor, ruxolitinib (Jakavi®), was approved. Since it was initially unclear what function these kinases fulfilled, they were given the name JAK: "Just Another Kinase". In the meantime, however, the name Janus kinase has become more common. This name is derived from the Roman god Janus, the god with two faces. Janus kinases also have "two faces": one directed outward and a second directed inward. Signals can be transmitted from the cell surface to the cell interior with the help of the Janus kinases.

Literature
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  1. Forster M et al.(2016) Selective JAK3 inhibitors with
    a Covalent Reversible Binding Mode Targeting a New Induced Fit Binding Pocket. Cell Chem Biol 23:1335-1340.

  2. Pieri L et al (2009) The JAK2V617 mutation induces constitutive activation and agonist hypersensitivity in basophils from patients with polycythemia vera. Haematologica 94:1537-1545

  3. Xing L et al (2014) Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med 20:1043-1049

Outgoing links (1)

Pruritus aquagener;

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Last updated on: 05.03.2021