BTK

Summary

Gene Symbol: BTK
Description: Bruton tyrosine kinase
Alias: AGMX1, ATK, BPK, IMD1, PSCTK1, XLA, tyrosine-protein kinase BTK, B-cell progenitor kinase, Bruton agammaglobulinemia tyrosine kinase, Bruton's tyrosine kinase, agammaglobulinaemia tyrosine kinase, dominant-negative kinase-deficient Brutons tyrosine kinase, truncated Bruton agammaglobulinemia tyrosine kinase, tyrosine-protein kinase BTK isoform (lacking exon 13 to 17), tyrosine-protein kinase BTK isoform (lacking exon 14)
Species: human
Products:     BTK

Top Publications

  1. Baraldi E, Djinovic Carugo K, Hyvonen M, Surdo P, Riley A, Potter B, et al. Structure of the PH domain from Bruton's tyrosine kinase in complex with inositol 1,3,4,5-tetrakisphosphate. Structure. 1999;7:449-60 pubmed
    ..of point mutations in this enzyme result in a severe human immunodeficiency known as X-linked agammaglobulinemia (XLA)...
  2. Hashimoto S, Iwamatsu A, Ishiai M, Okawa K, Yamadori T, Matsushita M, et al. 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. 1999;94:2357-64 pubmed
    Bruton's tyrosine kinase (Btk) is a critical component in the B-cell antigen receptor (BCR)-coupled signaling pathway. Its deficiency in B cells leads to loss or marked reduction in the BCR-induced calcium signaling...
  3. Stork B, Neumann K, Goldbeck I, Alers S, Kahne T, Naumann M, et al. Subcellular localization of Grb2 by the adaptor protein Dok-3 restricts the intensity of Ca2+ signaling in B cells. EMBO J. 2007;26:1140-9 pubmed
    ..Hence, the Dok-3/Grb2 module is a membrane-associated signaling organizer, which orchestrates the interaction efficiency of Ca2+-mobilizing enzymes. ..
  4. Dinh M, Grunberger D, Ho H, Tsing S, Shaw D, Lee S, et al. Activation mechanism and steady state kinetics of Bruton's tyrosine kinase. J Biol Chem. 2007;282:8768-76 pubmed
    Bruton's tyrosine kinase (BTK) is a member of the Tec non-receptor tyrosine kinase family that is involved in regulating B cell proliferation...
  5. Laederach A, Cradic K, Brazin K, Zamoon J, Fulton D, Huang X, et al. Competing modes of self-association in the regulatory domains of Bruton's tyrosine kinase: intramolecular contact versus asymmetric homodimerization. Protein Sci. 2002;11:36-45 pubmed
    A nuclear magnetic resonance (NMR) investigation of a fragment of the nonreceptor Tec family tyrosine kinase Btk has revealed an intricate set of coupled monomer-dimer equilibria...
  6. Rushworth S, Murray M, Zaitseva L, Bowles K, MacEwan D. Identification of Bruton's tyrosine kinase as a therapeutic target in acute myeloid leukemia. Blood. 2014;123:1229-38 pubmed publisher
    Bruton's tyrosine kinase (BTK) is a cytoplasmic protein found in all hematopoietic cell lineages except for T cells. BTK mediates signaling downstream of a number of receptors...
  7. Gray P, Dunne A, Brikos C, Jefferies C, Doyle S, O Neill L. MyD88 adapter-like (Mal) is phosphorylated by Bruton's tyrosine kinase during TLR2 and TLR4 signal transduction. J Biol Chem. 2006;281:10489-95 pubmed
    ..We found that the Bruton's tyrosine kinase (Btk) inhibitor LFM-A13 could block the endogenous phosphorylation of Mal on tyrosine in cells treated with macrophage-..
  8. Tsukada S, Saffran D, Rawlings D, Parolini O, Allen R, Klisak I, et al. Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell. 1993;72:279-90 pubmed
    We describe a novel cytoplasmic tyrosine kinase, termed BPK (B cell progenitor kinase), which is expressed in all stages of the B lineage and in myeloid cells...
  9. Mahajan S, Vassilev A, Sun N, Ozer Z, Mao C, Uckun F. Transcription factor STAT5A is a substrate of Bruton's tyrosine kinase in B cells. J Biol Chem. 2001;276:31216-28 pubmed
    ..Here we show that STAT5A can serve as a functional substrate of Bruton's tyrosine kinase (BTK)...

More Information

Publications86

  1. Smith C, Baskin B, Humire Greiff P, Zhou J, Olsson P, Maniar H, et al. Expression of Bruton's agammaglobulinemia tyrosine kinase gene, BTK, is selectively down-regulated in T lymphocytes and plasma cells. J Immunol. 1994;152:557-65 pubmed
    ..protein-tyrosine kinases and is designated Btk (Bruton's agammaglobulinemia tyrosine kinase; formerly Atk/Bpk; the human gene is denoted BTK, using capital letters according to the kinase nomenclature)...
  2. Baba Y, Hashimoto S, Matsushita M, Watanabe D, Kishimoto T, Kurosaki T, et al. BLNK mediates Syk-dependent Btk activation. Proc Natl Acad Sci U S A. 2001;98:2582-6 pubmed
    b>Btk is a critical molecule in B cell antigen receptor (BCR)-coupled signaling, and its activity is regulated by Lyn and Syk...
  3. Herman S, Gordon A, Hertlein E, Ramanunni A, Zhang X, Jaglowski S, et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 2011;117:6287-96 pubmed publisher
    ..Bruton tyrosine kinase (BTK) is essential to BCR signaling and in knockout mouse models its mutation has a relatively B cell-specific phenotype...
  4. Middendorp S, Dingjan G, Maas A, Dahlenborg K, Hendriks R. Function of Bruton's tyrosine kinase during B cell development is partially independent of its catalytic activity. J Immunol. 2003;171:5988-96 pubmed
    The Tec family member Bruton's tyrosine kinase (Btk) is a cytoplasmic protein tyrosine kinase that transduces signals from the pre-B and B cell receptor (BCR)...
  5. Vihinen M, Belohradsky B, Haire R, Holinski Feder E, Kwan S, Lappalainen I, et al. BTKbase, mutation database for X-linked agammaglobulinemia (XLA). Nucleic Acids Res. 1997;25:166-71 pubmed
    ..is an immunodeficiency caused by mutations in the gene coding for Bruton's agammaglobulinemia tyrosine kinase (BTK)...
  6. Hendriks R, Kersseboom R. Involvement of SLP-65 and Btk in tumor suppression and malignant transformation of pre-B cells. Semin Immunol. 2006;18:67-76 pubmed
    ..In the mouse, the downstream signaling molecules SLP-65 and Btk cooperate to limit proliferation and induce differentiation of pre-B cells, thereby acting as tumor suppressors to ..
  7. Uckun F, Waddick K, Mahajan S, Jun X, Takata M, Bolen J, et al. BTK as a mediator of radiation-induced apoptosis in DT-40 lymphoma B cells. Science. 1996;273:1096-100 pubmed
    Bruton's tyrosine kinase (BTK) is a member of the SRC-related TEC family of protein tyrosine kinases (PTKs)...
  8. Liu W, Quinto I, Chen X, Palmieri C, Rabin R, Schwartz O, et al. Direct inhibition of Bruton's tyrosine kinase by IBtk, a Btk-binding protein. Nat Immunol. 2001;2:939-46 pubmed
    ..Btk deficiency causes X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency in mice...
  9. Goodman P, Wood C, Vassilev A, Mao C, Uckun F. Defective expression of Bruton's tyrosine kinase in acute lymphoblastic leukemia. Leuk Lymphoma. 2003;44:1011-8 pubmed
    Bruton's tyrosine kinase (BTK) is a cytoplasmic tyrosine kinase that serves an essential role in B cell signaling and development...
  10. Tai Y, Chang B, Kong S, Fulciniti M, Yang G, Calle Y, et al. Bruton tyrosine kinase inhibition is a novel therapeutic strategy targeting tumor in the bone marrow microenvironment in multiple myeloma. Blood. 2012;120:1877-87 pubmed publisher
    Bruton tyrosine kinase (Btk) has a well-defined role in B-cell development, whereas its expression in osteoclasts (OCs) further suggests a role in osteoclastogenesis...
  11. Mohamed A, Yu L, Bäckesjö C, Vargas L, Faryal R, Aints A, et al. Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Immunol Rev. 2009;228:58-73 pubmed publisher
    Bruton's agammaglobulinemia tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase important in B-lymphocyte development, differentiation, and signaling. Btk is a member of the Tec family of kinases...
  12. De Weers M, Mensink R, Kraakman M, Schuurman R, Hendriks R. Mutation analysis of the Bruton's tyrosine kinase gene in X-linked agammaglobulinemia: identification of a mutation which affects the same codon as is altered in immunodeficient xid mice. Hum Mol Genet. 1994;3:161-6 pubmed
    ..The gene defective in XLA has been identified as a cytoplasmic protein tyrosine kinase, named btk (Bruton's tyrosine kinase)...
  13. Chear C, Gill H, Ramly N, Dhaliwal J, Bujang N, Ripen A, et al. A novel Bruton's tyrosine kinase gene (BTK) invariant splice site mutation in a Malaysian family with X-linked agammaglobulinemia. Asian Pac J Allergy Immunol. 2013;31:320-4 pubmed publisher
    X-linked agammaglobulinemia (XLA) is a rare genetic disorder caused by mutations in the Bruton's tyrosine kinase (BTK) gene. These mutations cause defects in early B cell development...
  14. Su Y, Zhang Y, Schweikert J, Koretzky G, Reth M, Wienands J. Interaction of SLP adaptors with the SH2 domain of Tec family kinases. Eur J Immunol. 1999;29:3702-11 pubmed
    ..adaptors and involves phosphorylation of phospholipase C-gamma isoforms by the Tec-related protein tyrosine kinase Btk in B cells and Itk in T cells...
  15. Doyle S, Jefferies C, Feighery C, O Neill L. Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine kinase. J Biol Chem. 2007;282:36953-60 pubmed
    ..Finally we demonstrate that peripheral blood mononuclear cells from patients with X-linked agammaglobulinaemia (XLA) that have dysfunctional Btk are impaired in the induction of interleukin-6 by CpGB-DNA...
  16. Hansson H, Okoh M, Smith C, Vihinen M, Hard T. Intermolecular interactions between the SH3 domain and the proline-rich TH region of Bruton's tyrosine kinase. FEBS Lett. 2001;489:67-70 pubmed
    The SH3 domain of Bruton's tyrosine kinase (Btk) is preceded by the Tec homology (TH) region containing proline-rich sequences...
  17. Carpenter C. Btk-dependent regulation of phosphoinositide synthesis. Biochem Soc Trans. 2004;32:326-9 pubmed
    ..We found that Btk (Bruton's tyrosine kinase), a member of the Tec family of cytoplasmic protein tyrosine kinases, is constitutively ..
  18. Hyvonen M, Saraste M. Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: molecular explanations for X-linked agammaglobulinaemia. EMBO J. 1997;16:3396-404 pubmed
    ..It is a target for mutations causing X-linked agammaglobulinaemia (XLA) in man. We have determined the structure of the N-terminal part of Btk by X-ray crystallography at 1...
  19. Wang Y, Kanegane H, Wang X, Han X, Zhang Q, Zhao S, et al. Mutation of the BTK gene and clinical feature of X-linked agammaglobulinemia in mainland China. J Clin Immunol. 2009;29:352-6 pubmed publisher
    ..We investigated the gene mutation and clinical features of 30 Chinese X-linked agammaglobulinemia (XLA) patients from 27 families...
  20. Takahashi Tezuka M, Hibi M, Fujitani Y, Fukada T, Yamaguchi T, Hirano T. Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK. Oncogene. 1997;14:2273-82 pubmed
    Tec/Btk tyrosine kinases are members of a subgroup of Src tyrosine kinase family. They are reported to be activated in response to cytokines, such as IL-3 and IL-6...
  21. Vihinen M, Kwan S, Lester T, Ochs H, Resnick I, Valiaho J, et al. Mutations of the human BTK gene coding for bruton tyrosine kinase in X-linked agammaglobulinemia. Hum Mutat. 1999;13:280-5 pubmed
    ..agammaglobulinemia (XLA) is an immunodeficiency caused by mutations in the gene coding for Bruton agammaglobulinemia tyrosine kinase (BTK)...
  22. Doyle S, Jefferies C, O Neill L. Bruton's tyrosine kinase is involved in p65-mediated transactivation and phosphorylation of p65 on serine 536 during NFkappaB activation by lipopolysaccharide. J Biol Chem. 2005;280:23496-501 pubmed
    Bruton's tyrosine kinase (Btk) has recently been shown to participate in the induction of nuclear factor kappaB (NFkappaB)-dependent gene expression by the lipopolysaccharide (LPS) receptor Toll-like receptor-4 (TLR4)...
  23. Novina C, Kumar S, Bajpai U, Cheriyath V, Zhang K, Pillai S, et al. Regulation of nuclear localization and transcriptional activity of TFII-I by Bruton's tyrosine kinase. Mol Cell Biol. 1999;19:5014-24 pubmed
    Bruton's tyrosine kinase (Btk) is required for normal B-cell development, as defects in Btk lead to X-linked immunodeficiency (xid) in mice and X-linked agammaglobulinemia (XLA) in humans...
  24. Murayama K, Kato Murayama M, Mishima C, Akasaka R, Shirouzu M, Fukui Y, et al. Crystal structure of the Bruton's tyrosine kinase PH domain with phosphatidylinositol. Biochem Biophys Res Commun. 2008;377:23-8 pubmed publisher
    Bruton's tyrosine kinase (Btk) of the Tec family possesses a Pleckstrin homology (PH) domain, which is responsible for plasma membrane targeting...
  25. Yao L, Kawakami Y, Kawakami T. The pleckstrin homology domain of Bruton tyrosine kinase interacts with protein kinase C. Proc Natl Acad Sci U S A. 1994;91:9175-9 pubmed
    Bruton tyrosine kinase (EC 2.7.1.112) [Btk, encoded by Btk in mice and BTK in humans (formerly known as atk, BPK, or emb)], which is variously mutated in chromosome X-linked agammaglobulinemia patients and X-linked immunodeficient (xid) ..
  26. Jefferies C, Doyle S, Brunner C, Dunne A, Brint E, Wietek C, et al. Bruton's tyrosine kinase is a Toll/interleukin-1 receptor domain-binding protein that participates in nuclear factor kappaB activation by Toll-like receptor 4. J Biol Chem. 2003;278:26258-64 pubmed
    ..TLRs 4, 6, 8, and 9) as proteins to which the intracellular protein tyrosine kinase, Bruton's tyrosine kinase (Btk), binds...
  27. Bradley L, Sweatman A, Lovering R, Jones A, Morgan G, Levinsky R, et al. Mutation detection in the X-linked agammaglobulinemia gene, BTK, using single strand conformation polymorphism analysis. Hum Mol Genet. 1994;3:79-83 pubmed
    The gene defective in X-linked agammaglobulinemia (XLA) has recently been isolated and identified as btk, a non-receptor protein tyrosine kinase...
  28. Lee K, Shyur S, Chu S, Huang L, Kao Y, Lei W, et al. Clinical manifestations and BTK gene defect in 4 unrelated Taiwanese families with Bruton's disease. Asian Pac J Allergy Immunol. 2011;29:260-5 pubmed
    ..Here, we report the results of a BTK gene mutation screening study that was performed in Taiwanese families with the BTK gene defect to further ..
  29. Vetrie D, Vorechovsky I, Sideras P, Holland J, Davies A, Flinter F, et al. The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature. 1993;361:226-33 pubmed
    X-linked agammaglobulinaemia (XLA) is a human immunodeficiency caused by failure of pre-B cells in the bone marrow to develop into circulating mature B cells...
  30. Zheng B, Zhang Y, Jin Y, Yu H. A novel Bruton's tyrosine kinase gene (BTK) missense mutation in a Chinese family with X-linked agammaglobulinemia. BMC Pediatr. 2014;14:265 pubmed publisher
    X-linked agammaglobulinemia (XLA) is a rare inherited disease characterized by recurrent bacterial infections, a paucity or absence of peripheral lymphoid tissue, an absence of circulating B cells, and marked depression of serum IgG, IgA,..
  31. Tampella G, Kerns H, Niu D, Singh S, Khim S, Bosch K, et al. The Tec Kinase-Regulated Phosphoproteome Reveals a Mechanism for the Regulation of Inhibitory Signals in Murine Macrophages. J Immunol. 2015;195:246-56 pubmed publisher
    ..In the present study, we performed a detailed investigation of the role of the Tec kinases Btk and Tec kinases in regulating TLR signaling in several types of primary murine macrophages...
  32. Jamroziak K, Szymczyk A, Hus M, Wojciechowska M, Knopińska Posłuszny W, Hołojda J, et al. Hodgkin's variant of Richter's transformation during ibrutinib therapy in a series of CLL patients; the Polish Adult Leukemia Group report (PALG). Eur J Haematol. 2017;: pubmed publisher
    ..the Richter's transformation (Hodgkin-RT) when undergoing therapy with ibrutinib; a novel Bruton's tyrosine kinase (BTK) inhibitor...
  33. Johannes F, Hausser A, Storz P, Truckenmüller L, Link G, Kawakami T, et al. Bruton's tyrosine kinase (Btk) associates with protein kinase C mu. FEBS Lett. 1999;461:68-72 pubmed
    ..Mutational defects are associated with a severe immunodeficiency syndrome, X-chromosome linked agammaglobulinemia (XLA)...
  34. Ma C, Wong N, Rao G, Avery D, Torpy J, Hambridge T, et al. Monogenic mutations differentially affect the quantity and quality of T follicular helper cells in patients with human primary immunodeficiencies. J Allergy Clin Immunol. 2015;136:993-1006.e1 pubmed publisher
    ..PIDs resulting from mutations in STAT3, STAT1, TYK2, IL21, IL21R, IL10R, IFNGR1/2, IL12RB1, CD40LG, NEMO, ICOS, or BTK. Loss-of-function (LOF) mutations in STAT3, IL10R, CD40LG, NEMO, ICOS, or BTK reduced cTFH cell frequencies...
  35. Rothé B, Leal Esteban L, Bernet F, Urfer S, Doerr N, Weimbs T, et al. Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA. Mol Cell Biol. 2015;35:3339-53 pubmed publisher
    ..Importantly, aberrant C-terminal extension of the SAM domain in bpk mutant Bicc1 phenocopied these defects...
  36. Stiff A, Trikha P, Wesolowski R, Kendra K, Hsu V, Uppati S, et al. Myeloid-Derived Suppressor Cells Express Bruton's Tyrosine Kinase and Can Be Depleted in Tumor-Bearing Hosts by Ibrutinib Treatment. Cancer Res. 2016;76:2125-36 pubmed publisher
    ..Ibrutinib, an irreversible inhibitor of Bruton's tyrosine kinase (BTK) and IL2-inducible T-cell kinase (ITK), is in clinical use for the treatment of B-cell malignancies...
  37. Vihinen M, Zvelebil M, Zhu Q, Brooimans R, Ochs H, Zegers B, et al. Structural basis for pleckstrin homology domain mutations in X-linked agammaglobulinemia. Biochemistry. 1995;34:1475-81 pubmed
    Deficiencies in a tyrosine kinase, designated Btk, cause X-linked agammaglobulinemia (XLA) in man, a hereditary defect of B-cell differentiation...
  38. Grommes C, Pastore A, Palaskas N, Tang S, Campos C, Schartz D, et al. Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma. Cancer Discov. 2017;7:1018-1029 pubmed publisher
    Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-?B. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown...
  39. Feng L, Shen J, Feng C, Chen J, Wu Y. Comparison of radiofrequency kyphoplasty (RFK) and balloon kyphoplasty (BKP) in the treatment of vertebral compression fractures: A meta-analysis. Medicine (Baltimore). 2017;96:e7150 pubmed publisher
    ..subgroup analysis stratified by study design indicated that the incidence of leakage decreased 15% in RFK than BPK (P?<?.00001) in non-RCT subgroup, but RFK and BKP treatments were equivalent in the RCT studies (P? = ?.86)...
  40. Zhang Y, Wester L, He J, Geiger T, Moerkens M, Siddappa R, et al. IGF1R signaling drives antiestrogen resistance through PAK2/PIX activation in luminal breast cancer. Oncogene. 2018;37:1869-1884 pubmed publisher
    ..PAK-interacting exchange factors PIXα/β as downstream targets of IGF1R signaling, which are independent from PI3K/ATK and MAPK/ERK pathways. PAK2 and PIXα/β modulate IGF1R signaling-driven cell scattering...
  41. Rushworth S, Pillinger G, Abdul Aziz A, Piddock R, Shafat M, Murray M, et al. Activity of Bruton's tyrosine-kinase inhibitor ibrutinib in patients with CD117-positive acute myeloid leukaemia: a mechanistic study using patient-derived blast cells. Lancet Haematol. 2015;2:e204-11 pubmed publisher
    Roughly 80% of patients with acute myeloid leukaemia have high activity of Bruton's tyrosine-kinase (BTK) in their blast cells compared with normal haemopoietic cells, rendering the cells sensitive to the oral BTK inhibitor ibrutinib in ..
  42. Zhu Q, Zhang M, Winkelstein J, Chen S, Ochs H. Unique mutations of Bruton's tyrosine kinase in fourteen unrelated X-linked agammaglobulinemia families. Hum Mol Genet. 1994;3:1899-900 pubmed
  43. Ma Y, Huang X. Identification of the binding site for Gqalpha on its effector Bruton's tyrosine kinase. Proc Natl Acad Sci U S A. 1998;95:12197-201 pubmed
    ..Here, we demonstrate that G protein Gqalpha binds directly to the nonreceptor Bruton's tyrosine kinase (Btk) to a region composed of a Tec-homology (TH) domain and a sarcoma virus tyrosine kinase (Src)-homology 3 (SH3) ..
  44. Nixon J, Rajaiya J, Ayers N, Evetts S, Webb C. The transcription factor, Bright, is not expressed in all human B lymphocyte subpopulations. Cell Immunol. 2004;228:42-53 pubmed
    ..is tightly regulated and B cell-restricted and the Bright protein associates with Bruton's tyrosine kinase (Btk), the defective enzyme in X-linked immunodeficiency...
  45. Rohrer J, Parolini O, Belmont J, Conley M, Parolino O corrected to Parolini O. The genomic structure of human BTK, the defective gene in X-linked agammaglobulinemia. Immunogenetics. 1994;40:319-24 pubmed
    It has recently been demonstrated that mutations in the gene for Bruton's tyrosine kinase (BTK) are responsible for X-linked agammaglobulinemia...
  46. Kelly P, Romero D, Yang Y, Shaffer A, Chaudhary D, Robinson S, et al. Selective interleukin-1 receptor-associated kinase 4 inhibitors for the treatment of autoimmune disorders and lymphoid malignancy. J Exp Med. 2015;212:2189-201 pubmed publisher
    ..IRAK4 inhibition suppressed tumor growth as a single agent, and in combination with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib or the Bcl-2 inhibitor ABT-199...
  47. Mansell A, Smith R, Doyle S, Gray P, Fenner J, Crack P, et al. Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation. Nat Immunol. 2006;7:148-55 pubmed
    ..We demonstrate here that after TLR2 and TLR4 stimulation Mal becomes phosphorylated by Bruton's tyrosine kinase (Btk) and then interacts with SOCS-1, which results in Mal polyubiquitination and subsequent degradation...
  48. Hendriks R, Yuvaraj S, Kil L. Targeting Bruton's tyrosine kinase in B cell malignancies. Nat Rev Cancer. 2014;14:219-32 pubmed publisher
    Bruton's tyrosine kinase (BTK) is a key component of B cell receptor (BCR) signalling and functions as an important regulator of cell proliferation and cell survival in various B cell malignancies...
  49. Chen K, Chen Y, He Z, Zhou L, Zhang L, Song L, et al. [Influence of Co-inhibiting mTORC2 and HSP90 on Proliferation Apoptosis of Multiple Myeloma Cells]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016;24:1086-90 pubmed publisher
    ..PBS), then the growth inhibition rate, morphologic changes, apoptosis rate and the expression of caspase 3 and ATK protein in U266 cells were compared and analyzed...
  50. Bam R, Venkateshaiah S, Khan S, Ling W, Randal S, Li X, et al. Role of Bruton's tyrosine kinase (BTK) in growth and metastasis of INA6 myeloma cells. Blood Cancer J. 2014;4:e234 pubmed publisher
    Bruton's tyrosine kinase (BTK) and the chemokine receptor CXCR4 are linked in various hematologic malignancies...
  51. Lee W, Huang J, Kuo M, Lin S, Chen L, Chen M, et al. Analysis of genetic defects in patients with the common variable immunodeficiency phenotype in a single Taiwanese tertiary care hospital. Ann Allergy Asthma Immunol. 2007;99:433-42 pubmed
    Seven known genetic defects, including Bruton tyrosine kinase (Btk), CD4OL, and signaling lymphocyte activation molecule-associated protein (SAP) (all X-linked) and inducible costimulator molecule (ICOS), transmembrane activator and ..
  52. Chen J, Kinoshita T, Sukbuntherng J, Chang B, Elias L. Ibrutinib Inhibits ERBB Receptor Tyrosine Kinases and HER2-Amplified Breast Cancer Cell Growth. Mol Cancer Ther. 2016;15:2835-2844 pubmed
    Ibrutinib is a potent, small-molecule Bruton tyrosine kinase (BTK) inhibitor developed for the treatment of B-cell malignancies. Ibrutinib covalently binds to Cys481 in the ATP-binding domain of BTK...
  53. Islam T, Lindvall J, Wennborg A, Brandén L, Rabbani H, Smith C. Expression profiling in transformed human B cells: influence of Btk mutations and comparison to B cell lymphomas using filter and oligonucleotide arrays. Eur J Immunol. 2002;32:982-93 pubmed
    ..compared EBV-transformed wild-type (WT) B cells from a healthy individual, WT1 and an X-linked agammaglobulinemia (XLA) patient cell line, XLA1, using the Clontech filters arrays. Eleven genes were > or =1...
  54. Ma H, Qazi S, Ozer Z, Zhang J, Ishkhanian R, Uckun F. Regulatory phosphorylation of Ikaros by Bruton's tyrosine kinase. PLoS ONE. 2013;8:e71302 pubmed publisher
    ..Here we provide genetic and biochemical evidence for a previously unknown function of Bruton's tyrosine kinase (BTK) as a partner and posttranslational regulator of Ikaros, a zinc finger-containing DNA-binding protein that plays a ..
  55. Tarafdar S, Poe J, Smithgall T. The accessory factor Nef links HIV-1 to Tec/Btk kinases in an Src homology 3 domain-dependent manner. J Biol Chem. 2014;289:15718-28 pubmed publisher
    ..Using bimolecular fluorescence complementation, we observed that Nef interacts with the Tec family members Bmx, Btk, and Itk but not Tec or Txk...
  56. Slinger E, Thijssen R, Kater A, Eldering E. Targeting antigen-independent proliferation in chronic lymphocytic leukemia through differential kinase inhibition. Leukemia. 2017;31:2601-2607 pubmed publisher
    ..Targeting JAKs, but not SYK, blocked CD40L/IL-21-induced proliferation. In contrast, PI3K, BTK as well as SYK inhibition prevented CpG-induced proliferation...
  57. Guinamard R, Aspenstrom P, Fougereau M, Chavrier P, Guillemot J. Tyrosine phosphorylation of the Wiskott-Aldrich syndrome protein by Lyn and Btk is regulated by CDC42. FEBS Lett. 1998;434:431-6 pubmed
    ..Lyn and the Bruton's tyrosine kinase (Btk), two protein tyrosine kinases involved in Fc epsilonRI-signaling phosphorylate WASp and interact with WASp in vivo...
  58. Ohashi Y, Tsuchiya S, Konno T. A new point mutation involving a highly conserved leucine in the Btk SH2 domain in a family with X linked agammaglobulinaemia. J Med Genet. 1995;32:77-8 pubmed
  59. Kim E, Hurtz C, Koehrer S, Wang Z, Balasubramanian S, Chang B, et al. Ibrutinib inhibits pre-BCR+ B-cell acute lymphoblastic leukemia progression by targeting BTK and BLK. Blood. 2017;129:1155-1165 pubmed publisher
    ..Here, we investigated the activity and mechanism of action of the BTK inhibitor ibrutinib in preclinical models of B-ALL...
  60. Holinski Feder E, Weiss M, Brandau O, Jedele K, Nore B, Backesjo C, et al. Mutation screening of the BTK gene in 56 families with X-linked agammaglobulinemia (XLA): 47 unique mutations without correlation to clinical course. Pediatrics. 1998;101:276-84 pubmed
    ..for mutation screening in the BTK (Bruton's tyrosine kinase) gene, we investigated 56 X-linked agammaglobulinemia (XLA) families...
  61. Li T, Rawlings D, Park H, Kato R, Witte O, Satterthwaite A. Constitutive membrane association potentiates activation of Bruton tyrosine kinase. Oncogene. 1997;15:1375-83 pubmed
    Mutations in the nonreceptor tyrosine kinase Btk result in the B cell immunodeficiencies X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice...
  62. Conley M, Fitch Hilgenberg M, Cleveland J, Parolini O, Rohrer J. Screening of genomic DNA to identify mutations in the gene for Bruton's tyrosine kinase. Hum Mol Genet. 1994;3:1751-6 pubmed
    Mutations in the gene for Bruton's tyrosine kinase (Btk) are responsible for X-linked agammaglobulinemia (XLA)...
  63. Zucha M, Wu A, Lee W, Wang L, Lin W, Yuan C, et al. Bruton's tyrosine kinase (Btk) inhibitor ibrutinib suppresses stem-like traits in ovarian cancer. Oncotarget. 2015;6:13255-68 pubmed
    According to a Prognoscan database, upregulation of Bruton's tyrosine kinase (Btk) is associated with low overall survival in ovarian cancer patients...
  64. Katerndahl C, Heltemes Harris L, Willette M, Henzler C, Frietze S, Yang R, et al. Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival. Nat Immunol. 2017;18:694-704 pubmed publisher
    ..in signaling components of the precursor to the B cell antigen receptor (pre-BCR), including defects in BLNK, BTK, PKCβ, NF-κB1 and IKAROS, to initiate B-ALL...
  65. Woyach J, Bojnik E, Ruppert A, Stefanovski M, Goettl V, Smucker K, et al. Bruton's tyrosine kinase (BTK) function is important to the development and expansion of chronic lymphocytic leukemia (CLL). Blood. 2014;123:1207-13 pubmed publisher
    ..Bruton's tyrosine kinase (BTK) shows constitutive activity in CLL and is the target of irreversible inhibition by ibrutinib, an orally ..
  66. Li Y, Franklin S, Zhang M, Vondriska T. Highly efficient purification of protein complexes from mammalian cells using a novel streptavidin-binding peptide and hexahistidine tandem tag system: application to Bruton's tyrosine kinase. Protein Sci. 2011;20:140-9 pubmed publisher
    ..We illustrate the application of this approach for the purification of human Bruton's tyrosine kinase (Btk), which results in highly efficient binding and elution of bait protein in both purification steps (>50% ..
  67. Corneth O, Klein Wolterink R, Hendriks R. BTK Signaling in B Cell Differentiation and Autoimmunity. Curr Top Microbiol Immunol. 2016;393:67-105 pubmed publisher
    ..Bruton's tyrosine kinase (BTK) as the gene defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) in 1993, our knowledge on the physiological function of BTK has expanded impressively...
  68. Fabbro S, Smith S, Dubovsky J, Gru A, Jones J. Panniculitis in Patients Undergoing Treatment With the Bruton Tyrosine Kinase Inhibitor Ibrutinib for Lymphoid Leukemias. JAMA Oncol. 2015;1:684-6 pubmed publisher
  69. Kim Y, Park K, Jang S, Lee K, Byun J, Suh K, et al. HM71224, a selective Bruton's tyrosine kinase inhibitor, attenuates the development of murine lupus. Arthritis Res Ther. 2017;19:211 pubmed publisher
    ..Bruton's tyrosine kinase (BTK) plays critical roles in B cell receptor-related and Fc receptor-related signaling...
  70. Kondo K, Shaim H, Thompson P, Burger J, Keating M, Estrov Z, et al. Ibrutinib modulates the immunosuppressive CLL microenvironment through STAT3-mediated suppression of regulatory B-cell function and inhibition of the PD-1/PD-L1 pathway. Leukemia. 2017;: pubmed publisher
    Ibrutinib, a covalent inhibitor of Bruton Tyrosine Kinase (BTK), is approved for treatment of patients with relapsed/refractory or treatment-naïve chronic lymphocytic leukemia (CLL)...
  71. Lou Y, Lopez F, Jiang Y, Han X, Brotherton C, Billedeau R, et al. Mitigation of reactive metabolite formation for a series of 3-amino-2-pyridone inhibitors of Bruton's tyrosine kinase (BTK). Bioorg Med Chem Lett. 2017;27:632-635 pubmed publisher
    ..describes our effort in addressing reactive metabolite issues for a series of 3-amino-2-pyridone inhibitors of BTK, e.g. compound 1 has a value of 459pmol/mg protein in the microsomal covalent binding assay...
  72. Henrickson S. Teaching an old pathway new tricks: Targeting BTK to block NLRP3. Sci Immunol. 2017;2: pubmed publisher
    A proteomics screen identified BTK as a novel inflammasome regulator and demonstrated that blocking BTK can inhibit inflammasome activity.
  73. Wolfromm A, Delarue R. [Lymphomas: A therapeutic update]. Rev Med Interne. 2017;38:685-690 pubmed publisher
    ..Finally the BTK inhibitor, ibrutinib developed in the LLC has established itself in the management of mantle cell lymphoma and ..
  74. Vargas Hernandez A, Lopez Herrera G, Maravillas Montero J, Vences Catalan F, Mogica Martínez D, Rojo Dominguez A, et al. Consequences of two naturally occurring missense mutations in the structure and function of Bruton agammaglobulinemia tyrosine kinase. IUBMB Life. 2012;64:346-53 pubmed publisher
    b>Bruton agammaglobulinemia tyrosine kinase (BTK) is a key protein in the B-cell receptor (BCR) signaling pathway and plays an essential role in the differentiation of B lymphocytes...
  75. Oellerich T, Mohr S, Corso J, Beck J, Döbele C, Braun H, et al. FLT3-ITD and TLR9 use Bruton tyrosine kinase to activate distinct transcriptional programs mediating AML cell survival and proliferation. Blood. 2015;125:1936-47 pubmed publisher
    ..Here, we analyzed the role of Bruton tyrosine kinase (BTK) in AML...
  76. Röck J, Schneider E, Grün J, Grützkau A, Kuppers R, Schmitz J, et al. CD303 (BDCA-2) signals in plasmacytoid dendritic cells via a BCR-like signalosome involving Syk, Slp65 and PLCgamma2. Eur J Immunol. 2007;37:3564-75 pubmed
    ..Here, we demonstrate that PDC express a signalosome similar to the BCR signalosome, consisting of Lyn, Syk, Btk, Slp65 (Blnk) and PLCgamma2. CD303 associates with the signaling adapter FcR gamma-chain...
  77. Ge Y, Wang C, Song S, Huang J, Liu Z, Li Y, et al. Identification of highly potent BTK and JAK3 dual inhibitors with improved activity for the treatment of B-cell lymphoma. Eur J Med Chem. 2018;143:1847-1857 pubmed publisher
    The BTK and JAK3 receptor tyrosine kinases are two validated and therapeutically amenable targets in the treatment of B-cell lymphomas...