Bruton's tyrosine kinase

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Bruton agammaglobulinemia tyrosine kinase
1bwn opm.png
PH domain of Bruton's tyrosine kinase dimer with bound lipids. Blue plane shows hydrocarbon boundary of the lipid bilayer
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols BTK ; AGMX1; AT; ATK; BPK; IMD1; PSCTK1; XLA
External IDs OMIM300300 MGI88216 HomoloGene30953 ChEMBL: 5251 GeneCards: BTK Gene
EC number 2.7.10.2
RNA expression pattern
PBB GE BTK 205504 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 695 12229
Ensembl ENSG00000010671 ENSMUSG00000031264
UniProt Q06187 P35991
RefSeq (mRNA) NM_000061 NM_013482
RefSeq (protein) NP_000052 NP_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.

Function[edit]

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[edit]

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.

Discovery[edit]

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

Interactions[edit]

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

See also[edit]

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


References[edit]

  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. doi:10.1016/j.cellimm.2004.03.004. PMID 15203319. 
  3. ^ a b Yasuda T, Tezuka T, Maeda A, Inazu T, Yamanashi Y, Gu H, Kurosaki T, Yamamoto T (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. 
  4. ^ Hashimoto S, Iwamatsu A, Ishiai M, Okawa K, Yamadori T, Matsushita M, Baba Y, Kishimoto T, Kurosaki T, Tsukada S (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, Mohamed AJ (March 2002). "Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx". J. Biol. Chem. 277 (11): 9351–7. doi:10.1074/jbc.M108537200. PMID 11751885. 
  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. 
  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. doi:10.1074/jbc.M303724200. PMID 14623887. 
  8. ^ Novina CD, Kumar S, Bajpai U, Cheriyath V, Zhang K, Pillai S, Wortis HH, Roy 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. 
  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. 
  11. ^ Johannes FJ, Hausser A, Storz P, Truckenmüller L, Link G, Kawakami T, Pfizenmaier K (November 1999). "Bruton's tyrosine kinase (Btk) associates with protein kinase C mu". FEBS Lett. 461 (1-2): 68–72. PMID 10561498. 
  12. ^ Matsushita M, Yamadori T, Kato S, Takemoto Y, Inazawa J, Baba Y, Hashimoto S, Sekine S, Arai S, Kunikata T, Kurimoto M, Kishimoto T, Tsukada S (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. doi:10.1006/bbrc.1998.8420. PMID 9571151. 
  13. ^ Yamadori T, Baba Y, Matsushita M, Hashimoto S, Kurosaki M, Kurosaki T, Kishimoto T, Tsukada S (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. 

Further reading[edit]

External links[edit]