Open Access Articles- Top Results for Bruton%27s tyrosine kinase

Bruton's tyrosine kinase

External IDsOMIM300300 MGI88216 HomoloGene30953 IUPHAR: 1948 ChEMBL: 5251 GeneCards: BTK Gene
EC number2.7.10.2
RNA expression pattern
File:PBB GE BTK 205504 at tn.png
More reference expression data
RefSeq (mRNA)NM_000061NM_013482
RefSeq (protein)NP_000052NP_038510
Location (UCSC)Chr HG1439_PATCH:
100.6 – 100.64 Mb
Chr X:
134.54 – 134.58 Mb
PubMed search[1][2]

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.


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.

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). 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.


Bruton's tyrosine kinase was discovered in 1993 and is named for Ogden Bruton, who first described XLA in 1952.[1]


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

See also

  • Ibrutinib (PCI-32765), a selective Bruton's tyrosine kinase inhibitor


  1. ^ a b X-Linked Agammaglobulinemia Patient and Family Handbook for The Primary Immune Diseases. Third Edition. 2001. Published by the Immune Deficiency Foundation.
  2. ^ Nixon JC, Rajaiya JB, Ayers N, Evetts S, Webb CF (March 2004). "The transcription factor, Bright, is not expressed in all human B lymphocyte subpopulations". Cell. Immunol. 228 (1): 42–53. PMID 15203319. doi:10.1016/j.cellimm.2004.03.004. 
  3. ^ a b Yasuda T, Tezuka T, Maeda A, Inazu T, Yamanashi Y, Gu H et al. (July 2002). "Cbl-b positively regulates Btk-mediated activation of phospholipase C-gamma2 in B cells". J. Exp. Med. 196 (1): 51–63. PMC 2194016. PMID 12093870. doi:10.1084/jem.20020068. 
  4. ^ Hashimoto S, Iwamatsu A, Ishiai M, Okawa K, Yamadori T, Matsushita M et al. (October 1999). "Identification of the SH2 domain binding protein of Bruton's tyrosine kinase as BLNK--functional significance of Btk-SH2 domain in B-cell antigen receptor-coupled calcium signaling". Blood 94 (7): 2357–64. PMID 10498607. 
  5. ^ Vargas L, Nore BF, Berglof A, Heinonen JE, Mattsson PT, Smith CI et al. (March 2002). "Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx". J. Biol. Chem. 277 (11): 9351–7. PMID 11751885. doi:10.1074/jbc.M108537200. 
  6. ^ Ma YC, Huang XY (October 1998). "Identification of the binding site for Gqalpha on its effector Bruton's tyrosine kinase". Proc. Natl. Acad. Sci. U.S.A. 95 (21): 12197–201. PMC 22808. PMID 9770463. doi:10.1073/pnas.95.21.12197. 
  7. ^ Sacristán C, Tussié-Luna MI, Logan SM, Roy AL (February 2004). "Mechanism of Bruton's tyrosine kinase-mediated recruitment and regulation of TFII-I". J. Biol. Chem. 279 (8): 7147–58. PMID 14623887. doi:10.1074/jbc.M303724200. 
  8. ^ Novina CD, Kumar S, Bajpai U, Cheriyath V, Zhang K, Pillai S et al. (July 1999). "Regulation of nuclear localization and transcriptional activity of TFII-I by Bruton's tyrosine kinase". Mol. Cell. Biol. 19 (7): 5014–24. PMC 84330. PMID 10373551. 
  9. ^ Yang W, Desiderio S (January 1997). "BAP-135, a target for Bruton's tyrosine kinase in response to B cell receptor engagement". Proc. Natl. Acad. Sci. U.S.A. 94 (2): 604–9. PMC 19560. PMID 9012831. doi:10.1073/pnas.94.2.604. 
  10. ^ Guo B, Kato RM, Garcia-Lloret M, Wahl MI, Rawlings DJ (August 2000). "Engagement of the human pre-B cell receptor generates a lipid raft-dependent calcium signaling complex". Immunity 13 (2): 243–53. PMID 10981967. doi:10.1016/s1074-7613(00)00024-8. 
  11. ^ Johannes FJ, Hausser A, Storz P, Truckenmüller L, Link G, Kawakami T et al. (November 1999). "Bruton's tyrosine kinase (Btk) associates with protein kinase C mu". FEBS Lett. 461 (1-2): 68–72. PMID 10561498. doi:10.1016/S0014-5793(99)01424-6. 
  12. ^ Matsushita M, Yamadori T, Kato S, Takemoto Y, Inazawa J, Baba Y et al. (April 1998). "Identification and characterization of a novel SH3-domain binding protein, Sab, which preferentially associates with Bruton's tyrosine kinase (BtK)". Biochem. Biophys. Res. Commun. 245 (2): 337–43. PMID 9571151. doi:10.1006/bbrc.1998.8420. 
  13. ^ Yamadori T, Baba Y, Matsushita M, Hashimoto S, Kurosaki M, Kurosaki T et al. (May 1999). "Bruton's tyrosine kinase activity is negatively regulated by Sab, the Btk-SH3 domain-binding protein". Proc. Natl. Acad. Sci. U.S.A. 96 (11): 6341–6. PMC 26883. PMID 10339589. doi:10.1073/pnas.96.11.6341. 

Further reading


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