Bruton's tyrosine kinase


Bruton's tyrosine kinase, also known as tyrosine-protein kinase BTK, is a tyrosine kinase that is encoded by the BTK gene in humans. BTK plays a crucial role in B cell development.

Structure

BTK contains five different protein interaction domains. These domains include an amino terminal pleckstrin homology domain, a proline-rich TEC homology domain, SRC homology domains SH2 and SH3, as well as a kinase domain with enzymatic activity.

Function

BTK plays a crucial role in B cell development as it is required for transmitting signals from the pre-B cell receptor that forms after successful immunoglobulin heavy chain rearrangement. It also has a role in mast cell activation through the high-affinity IgE receptor.
Btk contains a PH domain that binds phosphatidylinositol -trisphosphate. PIP3 binding induces Btk to phosphorylate phospholipase C, which in turn hydrolyzes PIP2, a phosphatidylinositol, into two second messengers, inositol triphosphate and diacylglycerol, 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 ; sometimes abbreviated to XLA and selective IgM deficiency. 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:
Various drugs that inhibit BTK are in clinical trials:
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: