Bruton's tyrosine kinase

BTK
Available structures
PDB	Ortholog search: PDBe RCSB
showList of PDB id codes
	1AWW, 1AWX, 1B55, 1BTK, 1BWN, 1K2P, 1QLY, 2GE9, 2Z0P, 3GEN, 3K54, 3OCS, 3OCT, 3P08, 3PIX, 3PIY, 3PIZ, 3PJ1, 3PJ2, 3PJ3, 4NWM, 4OT5, 4OT6, 4OTF, 4OTQ, 4OTR, 4RFY, 4RFZ, 4RG0, 4YHF, 4Z3V, 4ZLY, 4ZLZ, 5BPY, 5BQ0, 5FBN, 4RX5, 5FBO
Identifiers
Aliases	BTK, AGMX1, AT, ATK, BPK, IMD1, PSCTK1, XLA, Bruton tyrosine kinase, IGHD3
External IDs	OMIM: 300300 MGI: 88216 HomoloGene: 30953 GeneCards: BTK
showGene location (Human)
Chr.	X chromosome (human)
End	101,390,796 bp
showGene location (Mouse)
Chr.	X chromosome (mouse)
End	134,583,570 bp
showRNA expression pattern
	More reference expression data
showGene ontology
Molecular function	• metal ion binding; • nucleotide binding; • lipid binding; • signaling receptor binding; • identical protein binding; • protein kinase activity; • transferase activity; • kinase activity; • phosphatidylinositol-3,4,5-trisphosphate binding; • non-membrane spanning protein tyrosine kinase activity; • ATP binding; • GO:0001948 protein binding; • protein tyrosine kinase activity;
Cellular component	• cytoplasm; • nucleus; • membrane; • membrane raft; • extrinsic component of cytoplasmic side of plasma membrane; • GO:0016023 cytoplasmic vesicle; • cytosol; • plasma membrane; • perinuclear region of cytoplasm; • mast cell granule;
Biological process	• transmembrane receptor protein tyrosine kinase signaling pathway; • mesoderm development; • GO:0007243 intracellular signal transduction; • peptidyl-tyrosine autophosphorylation; • B cell activation; • positive regulation of NF-kappaB transcription factor activity; • transcription, DNA-templated; • positive regulation of B cell differentiation; • B cell receptor signaling pathway; • Fc-epsilon receptor signaling pathway; • regulation of cell population proliferation; • adaptive immune response; • apoptotic process; • peptidyl-tyrosine phosphorylation; • protein phosphorylation; • negative regulation of cytokine production; • MyD88-dependent toll-like receptor signaling pathway; • apoptotic signaling pathway; • calcium-mediated signaling; • I-kappaB kinase/NF-kappaB signaling; • innate immune response; • regulation of transcription, DNA-templated; • cell maturation; • immune system process; • regulation of B cell cytokine production; • regulation of B cell apoptotic process; • phosphorylation; • histamine secretion by mast cell; • response to organic substance; • positive regulation of type III hypersensitivity; • protein autophosphorylation; • cellular response to reactive oxygen species; • cellular response to molecule of fungal origin; • positive regulation of type I hypersensitivity; • B cell affinity maturation; • negative regulation of B cell proliferation; • cellular response to interleukin-7; • T cell receptor signaling pathway; • G protein-coupled receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	695
	12229
	ENSG00000010671
	ENSMUSG00000031264
	Q06187
	P35991
	NM_001287345; NM_000061; NM_001287344
	NM_013482
	NP_000052; NP_001274273; NP_001274274
	NP_038510
	Wikidata
View/Edit Human	View/Edit Mouse

Bruton's tyrosine kinase (abbreviated Btk or BTK), also known as tyrosine-protein kinase BTK, is a tyrosine kinase that is encoded by the BTK gene in humans. BTK plays a crucial role in B cell development.

Structure[]

BTK contains five different protein interaction domains. These domains include an amino terminal pleckstrin homology (PH) domain, a proline-rich TEC homology (TH) domain, SRC homology (SH) domains SH2 and SH3, as well as a kinase domain with enzymatic activity.^[5]

Function[]

BTK plays a crucial role in B cell development as it is required for transmitting signals from the pre-B cell receptor that forms after successful immunoglobulin heavy chain rearrangement.^[6] It also has a role in mast cell activation through the high-affinity IgE receptor.^[7]

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.^{[citation needed]}

Clinical significance[]

Mutations in the BTK gene are implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia); sometimes abbreviated to XLA and selective IgM deficiency.^[8] 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 (Xq21.3-q22).^[9] At least 400 mutations of the BTK gene have been identified.

BTK inhibitors[]

Approved drugs that inhibit BTK:

Ibrutinib (PCI-32765), a selective Bruton's tyrosine kinase inhibitor.
Acalabrutinib, approved in October 2017^[10] for relapsed mantle cell lymphoma
Zanubrutinib for mantle cell lymphoma.^[11] It can be taken orally.^[12]
Tirabrutinib, approved in March 2020 in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma.^[13]

Various drugs that inhibit BTK are in clinical trials:^[14]

Phase 3:
- Acalabrutinib, for relapsed chronic lymphocytic leukemia (CLL), 95% overall remission reported.
- Tolebrutinib, for multiple sclerosis.^[15]^[16]
Phase 2:
- for multiple sclerosis.^[17]^[18]
- ABBV-105 for systemic lupus erythematosus (SLE)^[19]
- Fenebrutinib (GDC-0853, RG7845) for rheumatoid arthritis, systemic lupus erythematosus and chronic spontaneous urticaria.^[20]
- (LOXO-305) for relapsed B-cell lymphoma or B-cell leukemia.^[21]
Phase 1:
- ONO-4059 for non-Hodgkin lymphoma and/or CLL.^[22] Renamed GS-4059 and now in trial NCT02457598.^[23]
- (AVL-292, CC-292) ^[24]
- HM71224 for autoimmune diseases, under development by Hanmi Pharmaceutical and Lilly as of 2015^[25]

Discovery[]

Bruton's tyrosine kinase was discovered in 1993 and is named for Ogden Bruton, who first described XLA in 1952.^[9]

Interactions[]

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

References[]

^ Jump up to: ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000010671 - Ensembl, May 2017
^ Jump up to: ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000031264 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Pal Singh S, Dammeijer F, Hendriks RW (February 2018). "Role of Bruton's tyrosine kinase in B cells and malignancies". Molecular Cancer. 17 (1): 57. doi:10.1186/s12943-018-0779-z. PMC 5817726. PMID 29455639.
^ Owen, Judith A.; Punt, Jenni; Stranford, Sharon A.; Jones, Patricia P. (2013). Kuby Immunology (7th ed.). New York: W.H. Freeman. p. 93. ISBN 978-14641-3784-6.
^ Turner, Helen; Kinet, Jean-Pierre (November 1999). "Signalling through the high-affinity IgE receptor FcεRI". Nature. 402 (S6760): 24–30. doi:10.1038/35037021. PMID 10586892.
^ Christoph, Geier (18 August 2018). "Hypomorphic Mutations in the BCR Signalosome Lead to Selective Immunoglobulin M Deficiency and Impaired B-cell Homeostasis". Frontiers in Immunology. 9: 2984. doi:10.3389/fimmu.2018.02984. PMC 6305442. PMID 30619340.
^ Jump up to: ^a ^b X-Linked Agammaglobulinemia Patient and Family Handbook for The Primary Immune Diseases. Third Edition. 2001. Published by the Immune Deficiency Foundation.
^ "FDA approves new treatment for adults with mantle cell lymphoma". 24 March 2020.
^ "FDA approves therapy to treat patients with relapsed and refractory mantle cell lymphoma supported by clinical trial results showing high response rate of tumor shrinkage". U.S. Food and Drug Administration (FDA) (Press release). 14 November 2019. Retrieved 15 November 2019.
^ BeiGene Announces Initiation of a Combination Trial of the BTK Inhibitor BGB-3111 with the PD-1 Antibody BGB-A317. June 2016
^ Dhillon, Sohita (2020). "Tirabrutinib: First Approval". Drugs. 80 (8): 835–840. doi:10.1007/s40265-020-01318-8. PMID 32382949. S2CID 218531327.
^ Astra Signals A Late Run On BTK Inhibition. Dec 2015
^ Dolgin, Elie (January 2021). "BTK blockers make headway in multiple sclerosis". Nature Biotechnology. 39 (1): 3–5. doi:10.1038/s41587-020-00790-7. ISSN 1087-0156. PMID 33432223.
^ National Institute of Neurological Disorders and Stroke (NINDS) (2021-04-23). "A Phase 2 Clinical Trial of Tolebrutinib, a Brain-penetrant Bruton s Tyrosine Kinase Inhibitor, for the Modulation of Chronically Inflamed White Matter Lesions in Multiple Sclerosis". Cite journal requires |journal= (help)
^ Montalban X, Arnold DL, Weber MS, et al. (June 2019). "Placebo-Controlled Trial of an Oral BTK Inhibitor in Multiple Sclerosis". N. Engl. J. Med. 380 (25): 2406–2417. doi:10.1056/NEJMoa1901981. PMID 31075187.
^ "A Study of Efficacy and Safety of M2951 in Subjects With Relapsing Multiple Sclerosis". ClinicalTrials.gov. 29 November 2016. Retrieved 28 March 2020.
^ "A Study to Investigate the Safety and Efficacy of ABBV-105 and Upadacitinib Given Alone or in Combination in Participants With Moderately to Severely Active Systemic Lupus Erythematosus - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2019-10-08.
^ "Genentech: Our Pipeline". www.gene.com. Retrieved 2020-10-10.
^ Mato AR, Shah NN, Jurczak W, et al. (March 2021). "Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study". The Lancet. 397 (10277): 892–901. doi:10.1016/S0140-6736(21)00224-5. PMID 33676628.
^ Clinical trial number NCT01659255 for "ONO-4059 Phase I Dose-escalation Study to Investigate the Safety and Tolerability of ONO-4059 Given as Monotherapy in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma and/or Chronic Lymphocytic Leukaemi" at ClinicalTrials.gov
^ "Novel BTK, PI3K Inhibitors on Horizon for Relapsed CLL. March 2016". Archived from the original on 2016-04-05. Retrieved 2016-03-22.
^ Clinical trial number NCT01351935 for "Escalating Dose Study in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia" at ClinicalTrials.gov
^ Garde, Damian (March 19, 2015). "Lilly inks a $690M deal to get its hands on an autoimmune drug". FierceBiotech.
^ 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.
^ Jump up to: ^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. doi:10.1084/jem.20020068. PMC 2194016. PMID 12093870.
^ 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. doi:10.1182/blood.V94.7.2357.419k40_2357_2364. PMID 10498607.
^ 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.
^ 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. Bibcode:1998PNAS...9512197M. doi:10.1073/pnas.95.21.12197. PMC 22808. PMID 9770463.
^ 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.
^ 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. doi:10.1128/mcb.19.7.5014. PMC 84330. PMID 10373551.
^ 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. Bibcode:1997PNAS...94..604Y. doi:10.1073/pnas.94.2.604. PMC 19560. PMID 9012831.
^ 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. doi:10.1016/s1074-7613(00)00024-8. PMID 10981967.
^ 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. doi:10.1016/S0014-5793(99)01424-6. PMID 10561498.
^ 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.
^ 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. Bibcode:1999PNAS...96.6341Y. doi:10.1073/pnas.96.11.6341. PMC 26883. PMID 10339589.

External links[]

GeneReviews/NCBI/NIH/UW entry on X-Linked or Brunton's Agammaglobulinemia
Bruton's+tyrosine+kinase at the US National Library of Medicine Medical Subject Headings (MeSH)
Human BTK genome location and BTK gene details page in the UCSC Genome Browser.
Overview of all the structural information available in the PDB for UniProt: Q06187 (Tyrosine-protein kinase BTK) at the PDBe-KB.

[refGRCh38Ensembl-1] Jump up to: ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000010671 - Ensembl, May 2017

[refGRCm38Ensembl-2] Jump up to: ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000031264 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Pal Singh S, Dammeijer F, Hendriks RW (February 2018). "Role of Bruton's tyrosine kinase in B cells and malignancies". Molecular Cancer. 17 (1): 57. doi:10.1186/s12943-018-0779-z. PMC 5817726. PMID 29455639.

[6] Owen, Judith A.; Punt, Jenni; Stranford, Sharon A.; Jones, Patricia P. (2013). Kuby Immunology (7th ed.). New York: W.H. Freeman. p. 93. ISBN 978-14641-3784-6.

[7] Turner, Helen; Kinet, Jean-Pierre (November 1999). "Signalling through the high-affinity IgE receptor FcεRI". Nature. 402 (S6760): 24–30. doi:10.1038/35037021. PMID 10586892.

[8] Christoph, Geier (18 August 2018). "Hypomorphic Mutations in the BCR Signalosome Lead to Selective Immunoglobulin M Deficiency and Impaired B-cell Homeostasis". Frontiers in Immunology. 9: 2984. doi:10.3389/fimmu.2018.02984. PMC 6305442. PMID 30619340.

[IDF-9] Jump up to: ^a ^b X-Linked Agammaglobulinemia Patient and Family Handbook for The Primary Immune Diseases. Third Edition. 2001. Published by the Immune Deficiency Foundation.

[10] "FDA approves new treatment for adults with mantle cell lymphoma". 24 March 2020.

[FDA_PR-11] "FDA approves therapy to treat patients with relapsed and refractory mantle cell lymphoma supported by clinical trial results showing high response rate of tumor shrinkage". U.S. Food and Drug Administration (FDA) (Press release). 14 November 2019. Retrieved 15 November 2019.

[BEIG1606-12] BeiGene Announces Initiation of a Combination Trial of the BTK Inhibitor BGB-3111 with the PD-1 Antibody BGB-A317. June 2016

[Dhillon-13] Dhillon, Sohita (2020). "Tirabrutinib: First Approval". Drugs. 80 (8): 835–840. doi:10.1007/s40265-020-01318-8. PMID 32382949. S2CID 218531327.

[14] Astra Signals A Late Run On BTK Inhibition. Dec 2015

[15] Dolgin, Elie (January 2021). "BTK blockers make headway in multiple sclerosis". Nature Biotechnology. 39 (1): 3–5. doi:10.1038/s41587-020-00790-7. ISSN 1087-0156. PMID 33432223.

[16] National Institute of Neurological Disorders and Stroke (NINDS) (2021-04-23). "A Phase 2 Clinical Trial of Tolebrutinib, a Brain-penetrant Bruton s Tyrosine Kinase Inhibitor, for the Modulation of Chronically Inflamed White Matter Lesions in Multiple Sclerosis". Cite journal requires |journal= (help)

[17] Montalban X, Arnold DL, Weber MS, et al. (June 2019). "Placebo-Controlled Trial of an Oral BTK Inhibitor in Multiple Sclerosis". N. Engl. J. Med. 380 (25): 2406–2417. doi:10.1056/NEJMoa1901981. PMID 31075187.

[18] "A Study of Efficacy and Safety of M2951 in Subjects With Relapsing Multiple Sclerosis". ClinicalTrials.gov. 29 November 2016. Retrieved 28 March 2020.

[19] "A Study to Investigate the Safety and Efficacy of ABBV-105 and Upadacitinib Given Alone or in Combination in Participants With Moderately to Severely Active Systemic Lupus Erythematosus - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2019-10-08.

[20] "Genentech: Our Pipeline". www.gene.com. Retrieved 2020-10-10.

[21] Mato AR, Shah NN, Jurczak W, et al. (March 2021). "Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study". The Lancet. 397 (10277): 892–901. doi:10.1016/S0140-6736(21)00224-5. PMID 33676628.

[NCT01659255-22] Clinical trial number NCT01659255 for "ONO-4059 Phase I Dose-escalation Study to Investigate the Safety and Tolerability of ONO-4059 Given as Monotherapy in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma and/or Chronic Lymphocytic Leukaemi" at ClinicalTrials.gov

[Inman2016-23] "Novel BTK, PI3K Inhibitors on Horizon for Relapsed CLL. March 2016". Archived from the original on 2016-04-05. Retrieved 2016-03-22.

[NCT01351935-24] Clinical trial number NCT01351935 for "Escalating Dose Study in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia" at ClinicalTrials.gov

[25] Garde, Damian (March 19, 2015). "Lilly inks a $690M deal to get its hands on an autoimmune drug". FierceBiotech.

[pmid15203319-26] 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.

[pmid12093870-27] Jump up to: ^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. doi:10.1084/jem.20020068. PMC 2194016. PMID 12093870.

[pmid10498607-28] 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. doi:10.1182/blood.V94.7.2357.419k40_2357_2364. PMID 10498607.

[pmid11751885-29] 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.

[pmid9770463-30] 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. Bibcode:1998PNAS...9512197M. doi:10.1073/pnas.95.21.12197. PMC 22808. PMID 9770463.

[pmid14623887-31] 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.

[pmid10373551-32] 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. doi:10.1128/mcb.19.7.5014. PMC 84330. PMID 10373551.

[pmid9012831-33] 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. Bibcode:1997PNAS...94..604Y. doi:10.1073/pnas.94.2.604. PMC 19560. PMID 9012831.

[pmid10981967-34] 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. doi:10.1016/s1074-7613(00)00024-8. PMID 10981967.

[pmid10561498-35] 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. doi:10.1016/S0014-5793(99)01424-6. PMID 10561498.

[pmid9571151-36] 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.

[pmid10339589-37] 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. Bibcode:1999PNAS...96.6341Y. doi:10.1073/pnas.96.11.6341. PMC 26883. PMID 10339589.

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show v t Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)