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
PDB	1AWW, 1AWX, 1B55, 1BTK, 1BWN, 1K2P, 1QLY, 2GE9, 2Z0P, 3GEN, 3K54, 3OCS, 3OCT, 3P08, 3PIX, 3PIY, 3PIZ, 3PJ1, 3PJ2, 3PJ3
Identifiers
Symbols	BTK; AGMX1; AT; ATK; BPK; IMD1; PSCTK1; XLA
External IDs	OMIM: 300300 MGI: 88216 HomoloGene: 30953 GeneCards: BTK Gene
EC number	2.7.10.2
Gene Ontology
Molecular function	• nucleotide binding; • protein tyrosine kinase activity; • protein tyrosine kinase activity; • non-membrane spanning protein tyrosine kinase activity; • protein binding; • ATP binding; • ATP binding; • phosphatidylinositol-3,4,5-trisphosphate binding; • lipid binding; • identical protein binding; • metal ion binding;
Cellular component	• nucleus; • cytoplasm; • cytosol; • cytosol; • plasma membrane; • plasma membrane; • cytoplasmic vesicle; • membrane raft;
Biological process	• adaptive immune response; • regulation of B cell cytokine production; • regulation of B cell apoptosis; • regulation of transcription, DNA-dependent; • protein phosphorylation; • apoptotic process; • I-kappaB kinase/NF-kappaB cascade; • mesoderm development; • induction of apoptosis by extracellular signals; • peptidyl-tyrosine phosphorylation; • calcium-mediated signaling; • intracellular signal transduction; • intracellular signal transduction; • B cell activation; • innate immune response; • positive regulation of B cell differentiation; • cell maturation; • B cell receptor signaling pathway; • positive regulation of NF-kappaB transcription factor activity;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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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 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 messagers, inositol triphosphate (IP3) and diacylglycerol (DAG), which then go on to modulate the activity of downstream proteins during B-cell signalling. Patients often have sinopulmonary infections beginning 6 months after birth (maternally derived antibodies offer some protection until that time).

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

[edit] 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]

[edit] See also

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

[edit] References

^ ^a ^b X-Linked Agammaglobulinemia Patient and Family Handbook for The Primary Immune Diseases. Third Edition. 2001. Published by the Immune Deficiency Foundation.
^ 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. doi:10.1073/pnas.95.21.12197. ISSN 0027-8424. PMC 22808. PMID 9770463. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=22808.
^ ^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. doi:10.1084/jem.20020068. ISSN 0022-1007. PMC 2194016. PMID 12093870. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2194016.
^ 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. doi:10.1016/S1074-7613(00)00024-8. ISSN 1074-7613. PMID 10981967.
^ 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. doi:10.1016/S0014-5793(99)01424-6. ISSN 0014-5793. PMID 10561498.
^ 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.
^ 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.
^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=26883.
^ 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.
^ 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.
^ 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.
^ 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. PMC 84330. PMID 10373551. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84330.
^ 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. doi:10.1073/pnas.94.2.604. ISSN 0027-8424. PMC 19560. PMID 9012831. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=19560.

[edit] External links

[edit] Further reading

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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[IDF-0] X-Linked Agammaglobulinemia Patient and Family Handbook for The Primary Immune Diseases. Third Edition. 2001. Published by the Immune Deficiency Foundation.

[pmid9770463-1] 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. doi:10.1073/pnas.95.21.12197. ISSN 0027-8424. PMC 22808. PMID 9770463. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=22808.

[pmid12093870-2] 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. doi:10.1084/jem.20020068. ISSN 0022-1007. PMC 2194016. PMID 12093870. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2194016.

[pmid10981967-3] 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. doi:10.1016/S1074-7613(00)00024-8. ISSN 1074-7613. PMID 10981967.

[pmid10561498-4] 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. doi:10.1016/S0014-5793(99)01424-6. ISSN 0014-5793. PMID 10561498.

[pmid10498607-5] 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.

[pmid9571151-6] 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.

[pmid10339589-7] 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=26883.

[pmid11751885-8] 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.

[pmid15203319-9] 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.

[pmid14623887-10] 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.

[pmid10373551-11] 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. PMC 84330. PMID 10373551. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84330.

[pmid9012831-12] 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. doi:10.1073/pnas.94.2.604. ISSN 0027-8424. PMC 19560. PMID 9012831. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=19560.

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Bruton's tyrosine kinase

Contents

[edit] Interactions

[edit] See also

[edit] References

[edit] External links

[edit] Further reading

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