Bruton's tyrosine kinase

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
1aww, 1awx, 1b55, 1btk, 1bwn, 1k2p, 1qly, 2ge9
Identifiers
Symbols	BTK; AGMX1; AT; ATK; BPK; IMD1; MGC126261; MGC126262; PSCTK1; XLA
External IDs	OMIM: 300300 MGI: 88216 HomoloGene: 30953
Gene ontology Molecular function • nucleotide binding • protein-tyrosine kinase activity • protein binding • ATP binding • zinc ion binding • kinase activity • transferase activity • metal ion binding Cellular component • cytoplasm • cytoplasmic vesicle • lipid raft Biological process • protein amino acid phosphorylation • intracellular signaling cascade • I-kappaB kinase/NF-kappaB cascade • mesoderm development • induction of apoptosis by extracellular signals • peptidyl-tyrosine phosphorylation • calcium-mediated signaling
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	695	12229
Ensembl	ENSG00000010671	ENSMUSG00000031264
UniProt	Q06187	Q7TMU1
RefSeq	NM_000061 (mRNA)	NM_013482 (mRNA)
	NP_000052 (protein)	NP_038510 (protein)
Location	Chr X: 100.49 - 100.53 Mb	Chr X: 129.89 - 129.93 Mb
PubMed search	[1]	[2]

Bruton's tyrosine kinase (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 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]

External links

• UMich Orientation of Proteins in Membranes protein/pdbid-1bwn
• MeSH Bruton's+tyrosine+kinase

Interactions

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]

References

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 (Oct. 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. ISSN 0027-8424. PMID 9770463. 
3. ^ ^{a b} Yasuda, Tomoharu; Tezuka Tohru, Maeda Akito, Inazu Tetsuya, Yamanashi Yuji, Gu Hua, Kurosaki Tomohiro, Yamamoto Tadashi (Jul. 2002). "Cbl-b positively regulates Btk-mediated activation of phospholipase C-gamma2 in B cells". J. Exp. Med. (United States) 196 (1): 51–63. ISSN 0022-1007. PMID 12093870. 
4. ^ Guo, B; Kato R M, Garcia-Lloret M, Wahl M I, Rawlings D J (Aug. 2000). "Engagement of the human pre-B cell receptor generates a lipid raft-dependent calcium signaling complex". Immunity (UNITED STATES) 13 (2): 243–53. ISSN 1074-7613. PMID 10981967. 
5. ^ Johannes, F J; Hausser A, Storz P, Truckenmüller L, Link G, Kawakami T, Pfizenmaier K (Nov. 1999). "Bruton's tyrosine kinase (Btk) associates with protein kinase C mu". FEBS Lett. (NETHERLANDS) 461 (1-2): 68–72. 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 (Oct. 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 (Apr. 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. ISSN 0027-8424. PMID 10339589. 
9. ^ Vargas, Leonardo; Nore Beston F, Berglof Anna, Heinonen Juhana E, Mattsson Pekka T, Smith C I Edvard, Mohamed Abdalla J (Mar. 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 (Mar. 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 (Feb. 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 (Jul. 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. PMID 10373551. 
13. ^ Yang, W; Desiderio S (Jan. 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. ISSN 0027-8424. PMID 9012831. 

Further reading

v • d • e PDB Gallery 1aww: SH3 DOMAIN FROM BRUTON'S TYROSINE KINASE, NMR, 42 STRUCTURES   1awx: SH3 DOMAIN FROM BRUTON'S TYROSINE KINASE, NMR, MINIMIZED AVERAGE STRUCTURE   1b55: PH DOMAIN FROM BRUTON'S TYROSINE KINASE IN COMPLEX WITH INOSITOL 1,3,4,5-TETRAKISPHOSPHATE   1btk: PH DOMAIN AND BTK MOTIF FROM BRUTON'S TYROSINE KINASE MUTANT R28C   1bwn: PH DOMAIN AND BTK MOTIF FROM BRUTON'S TYROSINE KINASE MUTANT E41K IN COMPLEX WITH INS(1,3,4,5)P4   1k2p: Crystal structure of Bruton's tyrosine kinase domain   1qly: NMR STUDY OF THE SH3 DOMAIN FROM BRUTON'S TYROSINE KINASE, 20 STRUCTURES   2ge9: Solution Structures of the SH2 domain of Bruton's Tyrosine Kinase

This membrane protein-related article is a stub. You can help Wikipedia by expanding it. v • d • e