From Wikipedia, the free encyclopedia
Bruton's tyrosine kinase (or Btk) is a type of kinase enzyme implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (XLA). Its exact mechanism of action remains unknown, but it plays a crucial role in B cell maturation as well as mast cell activation through the high-affinity IgE receptor. 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.[1] 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.
Bruton's tyrosine kinase was discovered in 1993 and is named for Dr. Ogden Bruton, who first described XLA in 1952.[1]
[edit] External links
[edit] References
- ^ a b X-Linked Agammaglobulinemia Patient and Family Handbook for The Primary Immune Diseases. Third Edition. 2001. Published by the Immune Deficiency Foundation.
[edit] Further reading
- Ochs HD, Aruffo A (1994). "Advances in X-linked immunodeficiency diseases.". Curr. Opin. Pediatr. 5 (6): 684–91. PMID 7907259.
- Uckun FM (1998). "Bruton's tyrosine kinase (BTK) as a dual-function regulator of apoptosis.". Biochem. Pharmacol. 56 (6): 683–91. PMID 9751072.
- Tsubata T, Wienands J (2002). "B cell signaling. Introduction.". Int. Rev. Immunol. 20 (6): 675–8. PMID 11913944.
- Etzioni A (2002). "Novel aspects of hypogammaglobulinemic states.". Isr. Med. Assoc. J. 4 (4): 294–7. PMID 12001708.
- Niiro H, Clark EA (2003). "Branches of the B cell antigen receptor pathway are directed by protein conduits Bam32 and Carma1.". Immunity 19 (5): 637–40. PMID 14614850.
- Carpenter CL (2004). "Btk-dependent regulation of phosphoinositide synthesis.". Biochem. Soc. Trans. 32 (Pt 2): 326–9. doi:10.1042/. PMID 15046600.
- Hendriks RW, Kersseboom R (2006). "Involvement of SLP-65 and Btk in tumor suppression and malignant transformation of pre-B cells.". Semin. Immunol. 18 (1): 67–76. doi:10.1016/j.smim.2005.10.002. PMID 16300960.
