Bruton'S Tyrosine Kinase (Btk)

Bruton's tyrosine kinase (or Btk) is a type of kinase enzyme implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). 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 contains a PH domain which 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 messagers, inositol triphosphate (IP3) and diacylglycerol(DAG), which then go on to modulate the activity of downstream proteins during B-cell signalling.