Bruton's tyrosine kinase

Bruton's tyrosine kinase

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. [http://www.immunedisease.com/US/patients/IDF/agamma.html X-Linked Agammaglobulinemia] Patient and Family Handbook for The Primary Immune Diseases. Third Edition. 2001. Published by the Immune Deficiency Foundation.] 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.

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References

Further reading

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citations =
*cite journal | author=Ochs HD, Aruffo A |title=Advances in X-linked immunodeficiency diseases. |journal=Curr. Opin. Pediatr. |volume=5 |issue= 6 |pages= 684–91 |year= 1994 |pmid= 7907259 |doi=
*cite journal | author=Uckun FM |title=Bruton's tyrosine kinase (BTK) as a dual-function regulator of apoptosis. |journal=Biochem. Pharmacol. |volume=56 |issue= 6 |pages= 683–91 |year= 1998 |pmid= 9751072 |doi=
*cite journal | author=Tsubata T, Wienands J |title=B cell signaling. Introduction. |journal=Int. Rev. Immunol. |volume=20 |issue= 6 |pages= 675–8 |year= 2002 |pmid= 11913944 |doi=
*cite journal | author=Etzioni A |title=Novel aspects of hypogammaglobulinemic states. |journal=Isr. Med. Assoc. J. |volume=4 |issue= 4 |pages= 294–7 |year= 2002 |pmid= 12001708 |doi=
*cite journal | author=Niiro H, Clark EA |title=Branches of the B cell antigen receptor pathway are directed by protein conduits Bam32 and Carma1. |journal=Immunity |volume=19 |issue= 5 |pages= 637–40 |year= 2003 |pmid= 14614850 |doi=
*cite journal | author=Carpenter CL |title=Btk-dependent regulation of phosphoinositide synthesis. |journal=Biochem. Soc. Trans. |volume=32 |issue= Pt 2 |pages= 326–9 |year= 2004 |pmid= 15046600 |doi= 10.1042/
*cite journal | author=Hendriks RW, Kersseboom R |title=Involvement of SLP-65 and Btk in tumor suppression and malignant transformation of pre-B cells. |journal=Semin. Immunol. |volume=18 |issue= 1 |pages= 67–76 |year= 2006 |pmid= 16300960 |doi= 10.1016/j.smim.2005.10.002

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