Rahul Sharma (Editor)

Bruton's tyrosine kinase

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Covid-19
Species  Human
Entrez  695
Human  Mouse
Ensembl  ENSG00000010671
Bruton's tyrosine kinase
Aliases  BTK, AGMX1, AT, ATK, BPK, IMD1, PSCTK1, XLA, Bruton tyrosine kinase
External IDs  OMIM: 300300 MGI: 88216 HomoloGene: 30953 GeneCards: BTK

Bruton's tyrosine kinase (abbreviated Btk or BTK) also known as tyrosine-protein kinase BTK is an enzyme that in humans is encoded by the BTK gene. BTK is a kinase that plays a crucial role in B-cell development.

Contents

Function

BTK plays a crucial role in B cell maturation as well as mast cell activation through the high-affinity IgE receptor.

Btk contains a PH domain that binds phosphatidylinositol (3,4,5)-trisphosphate (PIP3). PIP3 binding induces Btk to phosphorylate phospholipase C, which in turn hydrolyzes PIP2, a phosphatidylinositol, into two second messengers, inositol triphosphate (IP3) and diacylglycerol (DAG), which then go on to modulate the activity of downstream proteins during B-cell signalling.

Clinical significance

Mutations in the BTK gene are implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia); sometimes abbreviated to XLA. Patients with XLA have normal pre-B cell populations in their bone marrow but these cells fail to mature and enter the circulation. The Btk gene is located on the X chromosome. At least 400 mutations of the BTK gene have been identified.

BTK inhibitors

Approved drugs that inhibit BTK :

  • Ibrutinib (PCI-32765), a selective Bruton's tyrosine kinase inhibitor.
  • Various drugs that inhibit BTK are in clinical trials:

  • Phase 3:
  • Acalabrutinib, for relapsed CLL, 95% overall remission reported.
  • Phase 2:
  • Phase 1:
  • ONO-4059 for Non-Hodgkin's Lymphoma and/or CLL. Renamed GS-4059 and now in trial NCT02457598.
  • spebrutinib (AVL-292, CC-292)
  • BGB-3111 for CLL. It can be taken orally.
  • Discovery

    Bruton's tyrosine kinase was discovered in 1993 and is named for Ogden Bruton, who first described XLA in 1952.

    Interactions

    Bruton's tyrosine kinase has been shown to interact with:

    References

    Bruton's tyrosine kinase Wikipedia


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