1btk › Citations

Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: molecular explanations for X-linked agammaglobulinaemia.

Hyvönen M, Saraste M
EMBO J 16 3396-404 (1997)
Cited: 151 times
EuropePMC logo PMID: 9218782

Abstract

Bruton's tyrosine kinase (Btk) is an enzyme which is involved in maturation of B cells. 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 1.6 A resolution. This part of the kinase contains a pleckstrin homology (PH) domain and a Btk motif. The structure of the PH domain is similar to those published previously: a seven-stranded bent beta-sheet with a C-terminal alpha-helix. Individual point mutations within the Btk PH domain which cause XLA can be classified as either structural or functional in the light of the three-dimensional structure and biochemical data. All functional mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids. It is likely that these mutations inactivate the Btk pathway in cell signalling by reducing its affinity for inositol phosphates, which causes a failure in translocation of the kinase to the cell membrane. A small number of signalling proteins contain a Btk motif that always follows a PH domain in the sequence. This small module has a novel fold which is held together by a zinc ion bound by three conserved cysteines and a histidine. The Btk motif packs against the second half of the beta-sheet of the PH domain, forming a close contact with it. Our structure opens up new ways to study the role of the PH domain and Btk motif in the cellular function of Btk and the molecular basis of its dysfunction in XLA patients.

Reviews - 1btk mentioned but not cited (3)

  1. The role of Bruton's tyrosine kinase in autoimmunity and implications for therapy. Crofford LJ, Nyhoff LE, Sheehan JH, Kendall PL. Expert Rev Clin Immunol 12 763-773 (2016)
  2. The Src module: an ancient scaffold in the evolution of cytoplasmic tyrosine kinases. Shah NH, Amacher JF, Nocka LM, Kuriyan J. Crit Rev Biochem Mol Biol 53 535-563 (2018)
  3. Impact of the Protein Data Bank on antineoplastic approvals. Westbrook JD, Soskind R, Hudson BP, Burley SK. Drug Discov Today 25 837-850 (2020)

Articles - 1btk mentioned but not cited (21)

  1. Evaluating conformational free energies: the colony energy and its application to the problem of loop prediction. Xiang Z, Soto CS, Honig B. Proc Natl Acad Sci U S A 99 7432-7437 (2002)
  2. A systematic screen for protein-lipid interactions in Saccharomyces cerevisiae. Gallego O, Betts MJ, Gvozdenovic-Jeremic J, Maeda K, Matetzki C, Aguilar-Gurrieri C, Beltran-Alvarez P, Bonn S, Fernández-Tornero C, Jensen LJ, Kuhn M, Trott J, Rybin V, Müller CW, Bork P, Kaksonen M, Russell RB, Russell RB, Gavin AC. Mol Syst Biol 6 430 (2010)
  3. Spectrum of disease-causing mutations in protein secondary structures. Khan S, Vihinen M. BMC Struct Biol 7 56 (2007)
  4. Autoinhibition of Bruton's tyrosine kinase (Btk) and activation by soluble inositol hexakisphosphate. Wang Q, Vogan EM, Nocka LM, Rosen CE, Zorn JA, Harrison SC, Kuriyan J. Elife 4 (2015)
  5. Identification of a structurally novel BTK mutation that drives ibrutinib resistance in CLL. Sharma S, Galanina N, Guo A, Lee J, Kadri S, Van Slambrouck C, Long B, Wang W, Ming M, Furtado LV, Segal JP, Stock W, Venkataraman G, Tang WJ, Lu P, Wang YL. Oncotarget 7 68833-68841 (2016)
  6. Conformation of full-length Bruton tyrosine kinase (Btk) from synchrotron X-ray solution scattering. Márquez JA, Smith CI, Petoukhov MV, Lo Surdo P, Mattsson PT, Knekt M, Westlund A, Scheffzek K, Saraste M, Svergun DI. EMBO J 22 4616-4624 (2003)
  7. The Skap-hom dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch. Swanson KD, Tang Y, Ceccarelli DF, Poy F, Sliwa JP, Neel BG, Eck MJ. Mol Cell 32 564-575 (2008)
  8. Structural mechanism for Bruton's tyrosine kinase activation at the cell membrane. Wang Q, Pechersky Y, Sagawa S, Pan AC, Shaw DE. Proc Natl Acad Sci U S A 116 9390-9399 (2019)
  9. Bacterial pleckstrin homology domains: a prokaryotic origin for the PH domain. Xu Q, Bateman A, Finn RD, Abdubek P, Astakhova T, Axelrod HL, Bakolitsa C, Carlton D, Chen C, Chiu HJ, Chiu M, Clayton T, Das D, Deller MC, Duan L, Ellrott K, Ernst D, Farr CL, Feuerhelm J, Grant JC, Grzechnik A, Han GW, Jaroszewski L, Jin KK, Klock HE, Knuth MW, Kozbial P, Krishna SS, Kumar A, Marciano D, McMullan D, Miller MD, Morse AT, Nigoghossian E, Nopakun A, Okach L, Puckett C, Reyes R, Rife CL, Sefcovic N, Tien HJ, Trame CB, van den Bedem H, Weekes D, Wooten T, Hodgson KO, Wooley J, Elsliger MA, Deacon AM, Godzik A, Lesley SA, Wilson IA. J Mol Biol 396 31-46 (2010)
  10. Impact of genetic variation on three dimensional structure and function of proteins. Bhattacharya R, Rose PW, Burley SK, Prlić A. PLoS One 12 e0171355 (2017)
  11. Zinc-bundle structure of the essential RNA polymerase subunit RPB10 from Methanobacterium thermoautotrophicum. Mackereth CD, Arrowsmith CH, Edwards AM, McIntosh LP. Proc Natl Acad Sci U S A 97 6316-6321 (2000)
  12. Calmodulin and PI(3,4,5)P₃ cooperatively bind to the Itk pleckstrin homology domain to promote efficient calcium signaling and IL-17A production. Wang X, Boyken SE, Hu J, Xu X, Rimer RP, Shea MA, Shaw AS, Andreotti AH, Huang YH. Sci Signal 7 ra74 (2014)
  13. Conformational snapshots of Tec kinases during signaling. Joseph RE, Andreotti AH. Immunol Rev 228 74-92 (2009)
  14. Structure-Based Virtual Screening Reveals Ibrutinib and Zanubrutinib as Potential Repurposed Drugs against COVID-19. Kaliamurthi S, Selvaraj G, Selvaraj C, Singh SK, Wei DQ, Peslherbe GH. Int J Mol Sci 22 7071 (2021)
  15. Exploration of Novel Inhibitors for Bruton's Tyrosine Kinase by 3D QSAR Modeling and Molecular Dynamics Simulation. Bavi R, Kumar R, Choi L, Woo Lee K. PLoS One 11 e0147190 (2016)
  16. An Autoinhibitory Role for the Pleckstrin Homology Domain of Interleukin-2-Inducible Tyrosine Kinase and Its Interplay with Canonical Phospholipid Recognition. Devkota S, Joseph RE, Boyken SE, Fulton DB, Andreotti AH. Biochemistry 56 2938-2949 (2017)
  17. Systematic simulation of the interactions of pleckstrin homology domains with membranes. Le Huray KIP, Wang H, Sobott F, Kalli AC. Sci Adv 8 eabn6992 (2022)
  18. Computational Analysis of the Binding Specificities of PH Domains. Jiang Z, Liang Z, Shen B, Hu G. Biomed Res Int 2015 792904 (2015)
  19. Rescue of the aggregation prone Itk Pleckstrin Homology domain by two mutations derived from the related kinases, Btk and Tec. Boyken SE, Fulton DB, Andreotti AH. Protein Sci 21 1288-1297 (2012)
  20. Zn-Induced Interactions Between SARS-CoV-2 orf7a and BST2/Tetherin. Petrosino M, Stellato F, Chiaraluce R, Consalvi V, La Penna G, Pasquo A, Proux O, Rossi G, Morante S. ChemistryOpen 10 1133-1141 (2021)
  21. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)


Reviews citing this publication (39)

  1. Synthesis and function of 3-phosphorylated inositol lipids. Vanhaesebroeck B, Leevers SJ, Ahmadi K, Timms J, Katso R, Driscoll PC, Woscholski R, Parker PJ, Waterfield MD. Annu Rev Biochem 70 535-602 (2001)
  2. Signal-dependent membrane targeting by pleckstrin homology (PH) domains. Lemmon MA, Ferguson KM. Biochem J 350 Pt 1 1-18 (2000)
  3. Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Mohamed AJ, Yu L, Bäckesjö CM, Vargas L, Faryal R, Aints A, Christensson B, Berglöf A, Vihinen M, Nore BF, Smith CI. Immunol Rev 228 58-73 (2009)
  4. Role of Bruton's tyrosine kinase in B cells and malignancies. Pal Singh S, Dammeijer F, Hendriks RW. Mol Cancer 17 57 (2018)
  5. Targeting Bruton's tyrosine kinase in B cell malignancies. Hendriks RW, Yuvaraj S, Kil LP. Nat Rev Cancer 14 219-232 (2014)
  6. Tec family kinases in T lymphocyte development and function. Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL. Annu Rev Immunol 23 549-600 (2005)
  7. Pleckstrin homology domains: a common fold with diverse functions. Rebecchi MJ, Scarlata S. Annu Rev Biophys Biomol Struct 27 503-528 (1998)
  8. The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species. Smith CI, Islam TC, Mattsson PT, Mohamed AJ, Nore BF, Vihinen M. Bioessays 23 436-446 (2001)
  9. Signaling and subcellular targeting by membrane-binding domains. Hurley JH, Misra S. Annu Rev Biophys Biomol Struct 29 49-79 (2000)
  10. The Src, Syk, and Tec family kinases: distinct types of molecular switches. Bradshaw JM. Cell Signal 22 1175-1184 (2010)
  11. BTKbase: the mutation database for X-linked agammaglobulinemia. Väliaho J, Smith CI, Vihinen M. Hum Mutat 27 1209-1217 (2006)
  12. Pleckstrin homology (PH) like domains - versatile modules in protein-protein interaction platforms. Scheffzek K, Welti S. FEBS Lett 586 2662-2673 (2012)
  13. Tec kinases: a family with multiple roles in immunity. Yang WC, Collette Y, Nunès JA, Olive D. Immunity 12 373-382 (2000)
  14. Interaction domains: from simple binding events to complex cellular behavior. Pawson T, Raina M, Nash P. FEBS Lett 513 2-10 (2002)
  15. Diversity in protein recognition by PTB domains. Forman-Kay JD, Pawson T. Curr Opin Struct Biol 9 690-695 (1999)
  16. Specificity in pleckstrin homology (PH) domain membrane targeting: a role for a phosphoinositide-protein co-operative mechanism. Maffucci T, Falasca M. FEBS Lett 506 173-179 (2001)
  17. Phospholipid-binding protein domains. Bottomley MJ, Salim K, Panayotou G. Biochim Biophys Acta 1436 165-183 (1998)
  18. Bruton's tyrosine kinase controls a sustained calcium signal essential for B lineage development and function. Rawlings DJ. Clin Immunol 91 243-253 (1999)
  19. Bruton's tyrosine kinase--an integral protein of B cell development that also has an essential role in the innate immune system. López-Herrera G, Vargas-Hernández A, González-Serrano ME, Berrón-Ruiz L, Rodríguez-Alba JC, Espinosa-Rosales F, Santos-Argumedo L. J Leukoc Biol 95 243-250 (2014)
  20. Genetic basis of abnormal B cell development. Conley ME, Cooper MD. Curr Opin Immunol 10 399-406 (1998)
  21. Bruton's tyrosine kinase (BTK) as a dual-function regulator of apoptosis. Uckun FM. Biochem Pharmacol 56 683-691 (1998)
  22. Ibrutinib resistance in mantle cell lymphoma: clinical, molecular and treatment aspects. Hershkovitz-Rokah O, Pulver D, Lenz G, Shpilberg O. Br J Haematol 181 306-319 (2018)
  23. Role of Btk in B cell development and signaling. Desiderio S. Curr Opin Immunol 9 534-540 (1997)
  24. Inhibitors of BTK and ITK: state of the new drugs for cancer, autoimmunity and inflammatory diseases. Vargas L, Hamasy A, Nore BF, Smith CI. Scand J Immunol 78 130-139 (2013)
  25. B-cell receptor signaling inhibitors for treatment of autoimmune inflammatory diseases and B-cell malignancies. Puri KD, Di Paolo JA, Gold MR. Int Rev Immunol 32 397-427 (2013)
  26. Protein fold irregularities that hinder sequence analysis. Russell RB, Russell RB, Ponting CP. Curr Opin Struct Biol 8 364-371 (1998)
  27. Inositol phospholipids: translocation, translocation, translocation... Irvine R. Curr Biol 8 R557-9 (1998)
  28. Pleckstrin homology domain as an inositol compound binding module. Hirata M, Kanematsu T, Takeuchi H, Yagisawa H. Jpn J Pharmacol 76 255-263 (1998)
  29. Early B cell defects. Gaspar HB, Conley ME. Clin Exp Immunol 119 383-389 (2000)
  30. Bruton's Tyrosine Kinase and Its Isoforms in Cancer. Wang X, Kokabee L, Kokabee M, Conklin DS. Front Cell Dev Biol 9 668996 (2021)
  31. X-linked agammaglobulinemia: lack of mature B lineage cells caused by mutations in the Btk kinase. Smith CI, Bäckesjö CM, Berglöf A, Brandén LJ, Islam T, Mattsson PT, Mohamed AJ, Müller S, Nore B, Vihinen M. Springer Semin Immunopathol 19 369-381 (1998)
  32. The transcription factor, Bright, and immunoglobulin heavy chain expression. Webb CF. Immunol Res 24 149-161 (2001)
  33. Targeting Bruton's tyrosine kinase for the treatment of B cell associated malignancies and autoimmune diseases: Preclinical and clinical developments of small molecule inhibitors. Zhang Z, Zhang D, Liu Y, Yang D, Ran F, Wang ML, Zhao G. Arch Pharm (Weinheim) 351 e1700369 (2018)
  34. Bruton tyrosine kinase inhibitors in B-cell lymphoma: beyond the antitumour effect. Wang H, Guo H, Yang J, Liu Y, Liu X, Zhang Q, Zhou K. Exp Hematol Oncol 11 60 (2022)
  35. Reining in BTK: Interdomain Interactions and Their Importance in the Regulatory Control of BTK. Kueffer LE, Joseph RE, Andreotti AH. Front Cell Dev Biol 9 655489 (2021)
  36. Ibrutinib-Associated Cardiotoxicity: From the Pharmaceutical to the Clinical. Dong R, Yan Y, Zeng X, Lin N, Tan B. Drug Des Devel Ther 16 3225-3239 (2022)
  37. Diffusion-based determination of protein homodimerization on reconstituted membrane surfaces. Jepson TA, Chung JK. BMB Rep 54 157-163 (2021)
  38. Regulatory mechanisms triggered by enzyme interactions with lipid membrane surfaces. Yu J, Boehr DD. Front Mol Biosci 10 1306483 (2023)
  39. [ZAP genes: characterizing the protein structure of a new family of proliferation associated genes in the exocrine pancreas]. Günther R, Zill H, Schmidt WE, Fölsch UR. Med Klin (Munich) 94 233-238 (1999)

Articles citing this publication (88)

  1. SHIP modulates immune receptor responses by regulating membrane association of Btk. Bolland S, Pearse RN, Kurosaki T, Ravetch JV. Immunity 8 509-516 (1998)
  2. Identification and analysis of PH domain-containing targets of phosphatidylinositol 3-kinase using a novel in vivo assay in yeast. Isakoff SJ, Cardozo T, Andreev J, Li Z, Ferguson KM, Abagyan R, Lemmon MA, Aronheim A, Skolnik EY. EMBO J 17 5374-5387 (1998)
  3. High-resolution structure of the pleckstrin homology domain of protein kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate. Thomas CC, Deak M, Alessi DR, van Aalten DM. Curr Biol 12 1256-1262 (2002)
  4. Structure of a Ran-binding domain complexed with Ran bound to a GTP analogue: implications for nuclear transport. Vetter IR, Nowak C, Nishimoto T, Kuhlmann J, Wittinghofer A. Nature 398 39-46 (1999)
  5. Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change. Milburn CC, Deak M, Kelly SM, Price NC, Alessi DR, Van Aalten DM. Biochem J 375 531-538 (2003)
  6. Role of phosphatidylinositol 3' kinase and a downstream pleckstrin homology domain-containing protein in controlling chemotaxis in dictyostelium. Funamoto S, Milan K, Meili R, Firtel RA. J Cell Biol 153 795-810 (2001)
  7. Etk/Bmx, a tyrosine kinase with a pleckstrin-homology domain, is an effector of phosphatidylinositol 3'-kinase and is involved in interleukin 6-induced neuroendocrine differentiation of prostate cancer cells. Qiu Y, Robinson D, Pretlow TG, Kung HJ. Proc Natl Acad Sci U S A 95 3644-3649 (1998)
  8. A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. Walter HS, Rule SA, Dyer MJ, Karlin L, Jones C, Cazin B, Quittet P, Shah N, Hutchinson CV, Honda H, Duffy K, Birkett J, Jamieson V, Courtenay-Luck N, Yoshizawa T, Sharpe J, Ohno T, Abe S, Nishimura A, Cartron G, Morschhauser F, Fegan C, Salles G. Blood 127 411-419 (2016)
  9. BTK regulates PtdIns-4,5-P2 synthesis: importance for calcium signaling and PI3K activity. Saito K, Tolias KF, Saci A, Koon HB, Humphries LA, Scharenberg A, Rawlings DJ, Kinet JP, Carpenter CL. Immunity 19 669-678 (2003)
  10. Comprehensive identification of PIP3-regulated PH domains from C. elegans to H. sapiens by model prediction and live imaging. Park WS, Heo WD, Whalen JH, O'Rourke NA, Bryan HM, Meyer T, Teruel MN. Mol Cell 30 381-392 (2008)
  11. Structure of the PH domain from Bruton's tyrosine kinase in complex with inositol 1,3,4,5-tetrakisphosphate. Baraldi E, Djinovic Carugo K, Hyvönen M, Surdo PL, Riley AM, Potter BV, O'Brien R, Ladbury JE, Saraste M. Structure 7 449-460 (1999)
  12. Dual targeting of Osh1p, a yeast homologue of oxysterol-binding protein, to both the Golgi and the nucleus-vacuole junction. Levine TP, Munro S. Mol Biol Cell 12 1633-1644 (2001)
  13. Phosphatidylinositol 3-kinase-gamma activates Bruton's tyrosine kinase in concert with Src family kinases. Li Z, Wahl MI, Eguinoa A, Stephens LR, Hawkins PT, Witte ON. Proc Natl Acad Sci U S A 94 13820-13825 (1997)
  14. Chlamydial entry involves TARP binding of guanine nucleotide exchange factors. Lane BJ, Mutchler C, Al Khodor S, Grieshaber SS, Carabeo RA. PLoS Pathog 4 e1000014 (2008)
  15. Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain. Chen R, Kim O, Li M, Xiong X, Guan JL, Kung HJ, Chen H, Shimizu Y, Qiu Y. Nat Cell Biol 3 439-444 (2001)
  16. PKCbeta modulates antigen receptor signaling via regulation of Btk membrane localization. Kang SW, Wahl MI, Chu J, Kitaura J, Kawakami Y, Kato RM, Tabuchi R, Tarakhovsky A, Kawakami T, Turck CW, Witte ON, Rawlings DJ. EMBO J 20 5692-5702 (2001)
  17. Vav2 is required for cell spreading. Marignani PA, Carpenter CL. J Cell Biol 154 177-186 (2001)
  18. Phosphorylation of two regulatory tyrosine residues in the activation of Bruton's tyrosine kinase via alternative receptors. Wahl MI, Fluckiger AC, Kato RM, Park H, Witte ON, Rawlings DJ. Proc Natl Acad Sci U S A 94 11526-11533 (1997)
  19. Regulation of nuclear localization and transcriptional activity of TFII-I by Bruton's tyrosine kinase. Novina CD, Kumar S, Bajpai U, Cheriyath V, Zhang K, Pillai S, Wortis HH, Roy AL. Mol Cell Biol 19 5014-5024 (1999)
  20. A novel B lymphocyte-associated adaptor protein, Bam32, regulates antigen receptor signaling downstream of phosphatidylinositol 3-kinase. Marshall AJ, Niiro H, Lerner CG, Yun TJ, Thomas S, Disteche CM, Clark EA. J Exp Med 191 1319-1332 (2000)
  21. Distinct subcellular localisations of the putative inositol 1,3,4,5-tetrakisphosphate receptors GAP1IP4BP and GAP1m result from the GAP1IP4BP PH domain directing plasma membrane targeting. Lockyer PJ, Bottomley JR, Reynolds JS, McNulty TJ, Venkateswarlu K, Potter BV, Dempsey CE, Cullen PJ. Curr Biol 7 1007-1010 (1997)
  22. Bruton's tyrosine kinase: from X-linked agammaglobulinemia toward targeted therapy for B-cell malignancies. Ponader S, Burger JA. J Clin Oncol 32 1830-1839 (2014)
  23. The PH domain and the polybasic c domain of cytohesin-1 cooperate specifically in plasma membrane association and cellular function. Nagel W, Schilcher P, Zeitlmann L, Kolanus W. Mol Biol Cell 9 1981-1994 (1998)
  24. Mutations of the human BTK gene coding for bruton tyrosine kinase in X-linked agammaglobulinemia. Vihinen M, Kwan SP, Lester T, Ochs HD, Resnick I, Väliaho J, Conley ME, Smith CI. Hum Mutat 13 280-285 (1999)
  25. Structural analyses of CREB-CBP transcriptional activator-coactivator complexes by NMR spectroscopy: implications for mapping the boundaries of structural domains. Radhakrishnan I, Pérez-Alvarado GC, Parker D, Dyson HJ, Montminy MR, Wright PE. J Mol Biol 287 859-865 (1999)
  26. A specific intermolecular association between the regulatory domains of a Tec family kinase. Brazin KN, Fulton DB, Andreotti AH. J Mol Biol 302 607-623 (2000)
  27. The transcription factor Bright associates with Bruton's tyrosine kinase, the defective protein in immunodeficiency disease. Webb CF, Yamashita Y, Ayers N, Evetts S, Paulin Y, Conley ME, Smith EA. J Immunol 165 6956-6965 (2000)
  28. BTKbase, mutation database for X-linked agammaglobulinemia (XLA). Vihinen M, Brandau O, Brandén LJ, Kwan SP, Lappalainen I, Lester T, Noordzij JG, Ochs HD, Ollila J, Pienaar SM, Riikonen P, Saha BK, Smith CI. Nucleic Acids Res 26 242-247 (1998)
  29. Identification of centaurin-alpha1 as a potential in vivo phosphatidylinositol 3,4,5-trisphosphate-binding protein that is functionally homologous to the yeast ADP-ribosylation factor (ARF) GTPase-activating protein, Gcs1. Venkateswarlu K, Oatey PB, Tavaré JM, Jackson TR, Cullen PJ. Biochem J 340 ( Pt 2) 359-363 (1999)
  30. Severe B cell deficiency and disrupted splenic architecture in transgenic mice expressing the E41K mutated form of Bruton's tyrosine kinase. Dingjan GM, Maas A, Nawijn MC, Smit L, Voerman JS, Grosveld F, Hendriks RW. EMBO J 17 5309-5320 (1998)
  31. A mutation in Bruton's tyrosine kinase as a cause of selective anti-polysaccharide antibody deficiency. Wood PM, Mayne A, Joyce H, Smith CI, Granoff DM, Kumararatne DS. J Pediatr 139 148-151 (2001)
  32. A mutation in the pleckstrin homology (PH) domain of the FGD1 gene in an Italian family with faciogenital dysplasia (Aarskog-Scott syndrome). Orrico A, Galli L, Falciani M, Bracci M, Cavaliere ML, Rinaldi MM, Musacchio A, Sorrentino V. FEBS Lett 478 216-220 (2000)
  33. De novo mutations from sporadic schizophrenia cases highlight important signaling genes in an independent sample. Kranz TM, Harroch S, Manor O, Lichtenberg P, Friedlander Y, Seandel M, Harkavy-Friedman J, Walsh-Messinger J, Dolgalev I, Heguy A, Chao MV, Malaspina D. Schizophr Res 166 119-124 (2015)
  34. RACK1, a protein kinase C scaffolding protein, interacts with the PH domain of p120GAP. Koehler JA, Moran MF. Biochem Biophys Res Commun 283 888-895 (2001)
  35. Achieving a Graded Immune Response: BTK Adopts a Range of Active/Inactive Conformations Dictated by Multiple Interdomain Contacts. Joseph RE, Wales TE, Fulton DB, Engen JR, Andreotti AH. Structure 25 1481-1494.e4 (2017)
  36. Defective degranulation and calcium mobilization of bone-marrow derived mast cells from Xid and Btk-deficient mice. Setoguchi R, Kinashi T, Sagara H, Hirosawa K, Takatsu K. Immunol Lett 64 109-118 (1998)
  37. Evolution of binding sites for zinc and calcium ions playing structural roles. Torrance JW, Macarthur MW, Thornton JM. Proteins 71 813-830 (2008)
  38. Proline isomerization preorganizes the Itk SH2 domain for binding to the Itk SH3 domain. Severin A, Joseph RE, Boyken S, Fulton DB, Andreotti AH. J Mol Biol 387 726-743 (2009)
  39. Bruton's tyrosine kinase (Btk) associates with protein kinase C mu. Johannes FJ, Hausser A, Storz P, Truckenmüller L, Link G, Kawakami T, Pfizenmaier K. FEBS Lett 461 68-72 (1999)
  40. Switch-like activation of Bruton's tyrosine kinase by membrane-mediated dimerization. Chung JK, Nocka LM, Decker A, Wang Q, Kadlecek TA, Weiss A, Kuriyan J, Groves JT. Proc Natl Acad Sci U S A 116 10798-10803 (2019)
  41. Competing modes of self-association in the regulatory domains of Bruton's tyrosine kinase: intramolecular contact versus asymmetric homodimerization. Laederach A, Cradic KW, Brazin KN, Zamoon J, Fulton DB, Huang XY, Andreotti AH. Protein Sci 11 36-45 (2002)
  42. Functional diversity of PH domains: an exhaustive modelling study. Blomberg N, Nilges M. Fold Des 2 343-355 (1997)
  43. Missense mutations affecting a conserved cysteine pair in the TH domain of Btk. Vihinen M, Nore BF, Mattsson PT, Bäckesjö CM, Nars M, Koutaniemi S, Watanabe C, Lester T, Jones A, Ochs HD, Smith CI. FEBS Lett 413 205-210 (1997)
  44. Stability and peptide binding specificity of Btk SH2 domain: molecular basis for X-linked agammaglobulinemia. Tzeng SR, Pai MT, Lung FD, Wu CW, Roller PP, Lei B, Wei CJ, Tu SC, Chen SH, Soong WJ, Cheng JW. Protein Sci 9 2377-2385 (2000)
  45. Multidomain Control Over TEC Kinase Activation State Tunes the T Cell Response. Andreotti AH, Joseph RE, Conley JM, Iwasa J, Berg LJ. Annu Rev Immunol 36 549-578 (2018)
  46. Phosphatidylinositol 3-phosphate-binding protein AtPH1 controls the localization of the metal transporter NRAMP1 in Arabidopsis. Agorio A, Giraudat J, Bianchi MW, Marion J, Espagne C, Castaings L, Lelièvre F, Curie C, Thomine S, Merlot S. Proc Natl Acad Sci U S A 114 E3354-E3363 (2017)
  47. Heteronuclear relaxation study of the PH domain of beta-spectrin: restriction of loop motions upon binding inositol trisphosphate. Gryk MR, Abseher R, Simon B, Nilges M, Oschkinat H. J Mol Biol 280 879-896 (1998)
  48. Structure of a PH domain from the C. elegans muscle protein UNC-89 suggests a novel function. Blomberg N, Baraldi E, Sattler M, Saraste M, Nilges M. Structure 8 1079-1087 (2000)
  49. Bruton's tyrosine kinase associates with the actin-based cytoskeleton in activated platelets. Mukhopadhyay S, Ramars AS, Dash D. J Cell Biochem 81 659-665 (2001)
  50. Itk: the rheostat of the T cell response. Grasis JA, Tsoukas CD. J Signal Transduct 2011 297868 (2011)
  51. Regulation of nucleocytoplasmic shuttling of Bruton's tyrosine kinase (Btk) through a novel SH3-dependent interaction with ankyrin repeat domain 54 (ANKRD54). Gustafsson MO, Hussain A, Mohammad DK, Mohamed AJ, Nguyen V, Metalnikov P, Colwill K, Pawson T, Smith CI, Nore BF. Mol Cell Biol 32 2440-2453 (2012)
  52. A single circularly permuted GFP sensor for inositol-1,3,4,5-tetrakisphosphate based on a split PH domain. Sakaguchi R, Endoh T, Yamamoto S, Tainaka K, Sugimoto K, Fujieda N, Kiyonaka S, Mori Y, Morii T. Bioorg Med Chem 17 7381-7386 (2009)
  53. Binding of a Pleckstrin homology domain protein to phosphoinositide in membranes: a miniaturized FRET-based assay for drug screening. Hamman BD, Pollok BA, Bennett T, Allen J, Heim R. J Biomol Screen 7 45-55 (2002)
  54. Engineering the phosphoinositide-binding profile of a class I pleckstrin homology domain. Cozier GE, Bouyoucef D, Cullen PJ. J Biol Chem 278 39489-39496 (2003)
  55. Exchange factor EFA6R requires C-terminal targeting to the plasma membrane to promote cytoskeletal rearrangement through the activation of ADP-ribosylation factor 6 (ARF6). Kanamarlapudi V. J Biol Chem 289 33378-33390 (2014)
  56. Pleckstrin homology domains of tec family protein kinases. Okoh MP, Vihinen M. Biochem Biophys Res Commun 265 151-157 (1999)
  57. Structural analyses of the Slm1-PH domain demonstrate ligand binding in the non-canonical site. Anand K, Maeda K, Gavin AC. PLoS One 7 e36526 (2012)
  58. The Tec family kinase Itk exists as a folded monomer in vivo. Qi Q, August A. J Biol Chem 284 29882-29892 (2009)
  59. Conserved domains subserve novel mechanisms and functions in DKF-1, a Caenorhabditis elegans protein kinase D. Feng H, Ren M, Rubin CS. J Biol Chem 281 17815-17826 (2006)
  60. Molecular modelling and site-directed mutagenesis of the inositol 1,3,4,5-tetrakisphosphate-binding pleckstrin homology domain from the Ras GTPase-activating protein GAP1IP4BP. Cozier G, Sessions R, Bottomley JR, Reynolds JS, Cullen PJ. Biochem J 349 333-342 (2000)
  61. Recombinant p42IP4, a brain-specific 42-kDa high-affinity Ins(1,3,4,5)P4 receptor protein, specifically interacts with lipid membranes containing Ptd-Ins(3,4,5)P3. Hanck T, Stricker R, Krishna UM, Falck JR, Chang YT, Chung SK, Reiser G. Eur J Biochem 261 577-584 (1999)
  62. X-chromosome inactivation and mutation pattern in the Bruton's tyrosine kinase gene in patients with X-linked agammaglobulinemia. Italian XLA Collaborative Group. Moschese V, Orlandi P, Plebani A, Arvanitidis K, Fiorini M, Speletas M, Mella P, Ritis K, Sideras P, Finocchi A, Livadiotti S, Rossi P. Mol Med 6 104-113 (2000)
  63. Lipid-targeting pleckstrin homology domain turns its autoinhibitory face toward the TEC kinases. Amatya N, Wales TE, Kwon A, Yeung W, Joseph RE, Fulton DB, Kannan N, Engen JR, Andreotti AH. Proc Natl Acad Sci U S A 116 21539-21544 (2019)
  64. Molecular and structural characterization of five novel mutations in the Bruton's tyrosine kinase gene from patients with X-linked agammaglobulinemia. Saha BK, Curtis SK, Vogler LB, Vihinen M. Mol Med 3 477-485 (1997)
  65. A Legionella effector kinase is activated by host inositol hexakisphosphate. Sreelatha A, Nolan C, Park BC, Pawłowski K, Tomchick DR, Tagliabracci VS. J Biol Chem 295 6214-6224 (2020)
  66. Crystal structure of the Bruton's tyrosine kinase PH domain with phosphatidylinositol. Murayama K, Kato-Murayama M, Mishima C, Akasaka R, Shirouzu M, Fukui Y, Yokoyama S. Biochem Biophys Res Commun 377 23-28 (2008)
  67. Interaction between Btk TH and SH3 domain. Okoh MP, Vihinen M. Biopolymers 63 325-334 (2002)
  68. Tissue-specific expression and endogenous subcellular distribution of the inositol 1,3,4,5-tetrakisphosphate-binding proteins GAP1(IP4BP) and GAP1(m). Lockyer PJ, Vanlingen S, Reynolds JS, McNulty TJ, Irvine RF, Parys JB, Cullen PJ. Biochem Biophys Res Commun 255 421-426 (1999)
  69. Distinct Roles for Bruton's Tyrosine Kinase in B Cell Immune Synapse Formation. Roman-Garcia S, Merino-Cortes SV, Gardeta SR, de Bruijn MJW, Hendriks RW, Carrasco YR. Front Immunol 9 2027 (2018)
  70. In vivo functional analysis of Drosophila Gap1: involvement of Ca2+ and IP4 regulation. Powe AC, Strathdee D, Cutforth T, D'Souza-Correia T, Gaines P, Thackeray J, Carlson J, Gaul U. Mech Dev 81 89-101 (1999)
  71. Comparative kinomics of human and chimpanzee reveal unique kinship and functional diversity generated by new domain combinations. Anamika K, Martin J, Srinivasan N. BMC Genomics 9 625 (2008)
  72. QSAR analysis of nicotinamidic compounds and design of potential Bruton's tyrosine kinase (Btk) inhibitors. Santos-Garcia L, Assis LC, Silva DR, Ramalho TC, da Cunha EF. J Biomol Struct Dyn 34 1421-1440 (2016)
  73. Recognizing the pleckstrin homology domain fold in mammalian phospholipase D using hidden Markov models. Holbrook PG, Geetha V, Beaven MA, Munson PJ. FEBS Lett 448 269-272 (1999)
  74. Decoding Ca2+ signals: a question of timing. Muallem S. J Cell Biol 170 173-175 (2005)
  75. Evaluating Acalabrutinib In The Treatment Of Mantle Cell Lymphoma: Design, Development, And Place In Therapy. Girard J, Reneau J, Devata S, Wilcox RA, Kaminski MS, Mercer J, Carty S, Phillips TJ. Onco Targets Ther 12 8003-8014 (2019)
  76. Molecular dynamic simulation to explore the molecular basis of Btk-PH domain interaction with Ins(1,3,4,5)P4. Lu D, Jiang J, Liang Z, Sun M, Luo C, Shen B, Hu G. ScientificWorldJournal 2013 580456 (2013)
  77. Mutations of Bruton's tyrosine kinase gene in Brazilian patients with X-linked agammaglobulinemia. Ramalho VD, Oliveira Júnior EB, Tani SM, Roxo Júnior P, Vilela MM. Braz J Med Biol Res 43 910-913 (2010)
  78. Rational design and purification of human Bruton's tyrosine kinase SH3-SH2 protein for structure-function studies. Nera KP, Brockmann E, Vihinen M, Smith CI, Mattsson PT. Protein Expr Purif 20 365-371 (2000)
  79. A conserved motif in the ITK PH-domain is required for phosphoinositide binding and TCR signaling but dispensable for adaptor protein interactions. Hirve N, Levytskyy RM, Rigaud S, Guimond DM, Zal T, Sauer K, Tsoukas CD. PLoS One 7 e45158 (2012)
  80. Computational studies of the binding profile of phosphoinositide PtdIns (3,4,5) P₃ with the pleckstrin homology domain of an oomycete cellulose synthase. Kuang G, Bulone V, Tu Y. Sci Rep 6 20555 (2016)
  81. Consequences of two naturally occurring missense mutations in the structure and function of Bruton agammaglobulinemia tyrosine kinase. Vargas-Hernández A, López-Herrera G, Maravillas-Montero JL, Vences-Catalán F, Mogica-Martínez D, Rojo-Domínguez A, Espinosa-Rosales FJ, Santos-Argumedo L. IUBMB Life 64 346-353 (2012)
  82. Palmitoylation of the Alternative Amino Terminus of the BTK-C Isoform Controls Subcellular Distribution and Signaling. Kokabee M, Wang X, Voorand E, Alin E, Kokabee L, Khan F, Desrosiers S, Conklin DS. Cancer Genomics Proteomics 19 415-427 (2022)
  83. A negative-feedback function of PKCβ in the formation and accumulation of signaling-active B cell receptor microclusters within B cell immunological synapse. Liu C, Zhao X, Xu L, Yi J, Shaheen S, Han W, Wang F, Zheng W, Xu C, Liu W. J Leukoc Biol 97 887-900 (2015)
  84. Context-dependent expression of a conditionally-inducible form of active Akt. Park S, Burke RE, Kareva T, Kholodilov N, Aimé P, Franke TF, Levy O, Greene LA. PLoS One 13 e0197899 (2018)
  85. Evolutionary relationship between the cysteine and histidine rich domains (CHORDs) and Btk-type zinc fingers. Kaur G, Subramanian S. Bioinformatics 34 1981-1985 (2018)
  86. Discovery of Novel Bruton's Tyrosine Kinase PROTACs with Enhanced Selectivity and Cellular Efficacy. Li YQ, Lannigan WG, Davoodi S, Daryaee F, Corrionero A, Alfonso P, Rodriguez-Santamaria JA, Wang N, Haley JD, Tonge PJ. J Med Chem 66 7454-7474 (2023)
  87. Stimulation of the catalytic activity of the tyrosine kinase Btk by the adaptor protein Grb2. Nocka LM, Eisen TJ, Iavarone AT, Groves JT, Kuriyan J. Elife 12 e82676 (2023)
  88. Letter X-Linked Agammaglobulinemia Case with TH Domain Missense Mutation in Bruton Tyrosine Kinase. Agrebi N, Gentilcore G, Grivel JC, Alkhayer G, Hassoun J, Hassan A, Adeli M, Lo B. J Clin Immunol 41 825-828 (2021)


Quick links