Bruton's tyrosine kinase

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Bruton agammaglobulinemia tyrosine kinase

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 OMIM: 300300 MGI: 88216 HomoloGene: 30953 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]
This box:

Bruton's tyrosine kinase (abbreviated Btk or BTK) is a type of kinase enzyme implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). 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 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.

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

Contents

Interactions [edit]

Bruton's tyrosine kinase has been shown to interact with GNAQ,[2] PLCG2,[3][4] Protein kinase D1,[5] B-cell linker,[3][6] SH3BP5,[7][8] Caveolin 1,[9] ARID3A[10] and GTF2I.[11][12][13]

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. ^ Ma, Y C; Huang X Y (October 1998). "Identification of the binding site for Gqalpha on its effector Bruton's tyrosine kinase". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 95 (21): 12197–201. doi:10.1073/pnas.95.21.12197. ISSN 0027-8424. PMC 22808. PMID 9770463. 
  3. ^ a b Yasuda, Tomoharu; Tezuka Tohru, Maeda Akito, Inazu Tetsuya, Yamanashi Yuji, Gu Hua, Kurosaki Tomohiro, Yamamoto Tadashi (July 2002). "Cbl-b positively regulates Btk-mediated activation of phospholipase C-gamma2 in B cells". J. Exp. Med. (United States) 196 (1): 51–63. doi:10.1084/jem.20020068. ISSN 0022-1007. PMC 2194016. PMID 12093870. 
  4. ^ Guo, B; Kato R M, Garcia-Lloret M, Wahl M I, Rawlings D J (August 2000). "Engagement of the human pre-B cell receptor generates a lipid raft-dependent calcium signaling complex". Immunity (UNITED STATES) 13 (2): 243–53. doi:10.1016/S1074-7613(00)00024-8. ISSN 1074-7613. PMID 10981967. 
  5. ^ Johannes, F J; 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. (NETHERLANDS) 461 (1-2): 68–72. doi:10.1016/S0014-5793(99)01424-6. ISSN 0014-5793. PMID 10561498. 
  6. ^ 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 (UNITED STATES) 94 (7): 2357–64. ISSN 0006-4971. PMID 10498607. 
  7. ^ 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. (UNITED STATES) 245 (2): 337–43. doi:10.1006/bbrc.1998.8420. ISSN 0006-291X. PMID 9571151. 
  8. ^ 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. (UNITED STATES) 96 (11): 6341–6. doi:10.1073/pnas.96.11.6341. ISSN 0027-8424. PMC 26883. PMID 10339589. 
  9. ^ Vargas, Leonardo; Nore Beston F, Berglof Anna, Heinonen Juhana E, Mattsson Pekka T, Smith C I Edvard, Mohamed Abdalla J (March 2002). "Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx". J. Biol. Chem. (United States) 277 (11): 9351–7. doi:10.1074/jbc.M108537200. ISSN 0021-9258. PMID 11751885. 
  10. ^ Nixon, Jamee C; Rajaiya Jaya B, Ayers Neil, Evetts Seth, Webb Carol F (March 2004). "The transcription factor, Bright, is not expressed in all human B lymphocyte subpopulations". Cell. Immunol. (United States) 228 (1): 42–53. doi:10.1016/j.cellimm.2004.03.004. ISSN 0008-8749. PMID 15203319. 
  11. ^ Sacristán, Catarina; Tussié-Luna María Isabel, Logan Sheila M, Roy Ananda L (February 2004). "Mechanism of Bruton's tyrosine kinase-mediated recruitment and regulation of TFII-I". J. Biol. Chem. (United States) 279 (8): 7147–58. doi:10.1074/jbc.M303724200. ISSN 0021-9258. PMID 14623887. 
  12. ^ Novina, C D; Kumar S, Bajpai U, Cheriyath V, Zhang K, Pillai S, Wortis H H, Roy A L (July 1999). "Regulation of nuclear localization and transcriptional activity of TFII-I by Bruton's tyrosine kinase". Mol. Cell. Biol. (UNITED STATES) 19 (7): 5014–24. ISSN 0270-7306. PMC 84330. PMID 10373551. 
  13. ^ 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. (UNITED STATES) 94 (2): 604–9. doi:10.1073/pnas.94.2.604. ISSN 0027-8424. PMC 19560. PMID 9012831. 

External links [edit]

Further reading [edit]

  • Ochs HD, Aruffo A (1994). "Advances in X-linked immunodeficiency diseases.". Curr. Opin. Pediatr. 5 (6): 684–91. doi:10.1097/00008480-199312000-00008. PMID 7907259. 
  • Uckun FM (1998). "Bruton's tyrosine kinase (BTK) as a dual-function regulator of apoptosis.". Biochem. Pharmacol. 56 (6): 683–91. doi:10.1016/S0006-2952(98)00122-1. 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. doi:10.1016/S1074-7613(03)00303-0. PMID 14614850. 
  • Carpenter CL (2004). "Btk-dependent regulation of phosphoinositide synthesis.". Biochem. Soc. Trans. 32 (Pt 2): 326–9. doi:10.1042/BST0320326. 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. 


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