Abstract
Bruton's tyrosine kinase (Btk), a cytoplasmic protein-tyrosine kinase, plays a pivotal role in B cell activation and development. Mutations in the pleckstrin homology (PH) domain of the Btk gene cause human X-linked agammaglobulinemia (XLA) and murine X-linked immunodeficiency (Xid). In this paper, we report that the PH domain of Btk functions as an inositol 1,3,4,5-tetrakisphosphate (IP4), inositol 1,3,4,5,6-pentakisphosphate, and inositol 1,2,3,4,5,6-hexakisphosphate (IP6) binding domain (Kd of approximately 40 nM for IP4), and that all of the XLA (Phe replaced by Ser at position 25 (F25S), R28H, T33P, V64F, and V113D) and Xid mutations (R28C) found in the PH domain result in a dramatic reduction of IP4 binding activity. Furthermore, the rare alternative splicing variant, with 33 amino acids deleted in the PH domain, corresponding to exon 3 of the Btk gene, also impaired IP4 binding capacity. In contrast, a gain-of-function mutant called Btk*, which carries a E41K mutation in the PH domain, binds IP6 with two times higher affinity than the wild type. Our data suggest that B cell differentiation is closely correlated with the IP4 binding capacity of the PH domain of Btk.
References
Dec 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J D SilicianoS V Desiderio
Mar 20, 1992·Cell·U GaulG M Rubin
May 26, 1994·Biochimica Et Biophysica Acta·J C MountfordG Brown
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·L YaoT Kawakami
May 1, 1995·Immunity·T LiO N Witte
Nov 3, 1995·The Journal of Biological Chemistry·M FukudaK Mikoshiba
Aug 10, 1995·Nature·P J CullenR F Irvine
Oct 1, 1994·Molecular and Cellular Biology·M MaekawaS Hattori
Nov 8, 1994·Proceedings of the National Academy of Sciences of the United States of America·S TsukadaA Katz
Aug 22, 1994·FEBS Letters·M VihinenC I Smith
Sep 1, 1993·Trends in Biochemical Sciences·A MusacchioM Saraste
Jul 16, 1993·Science·J D ThomasW E Paul
Jul 16, 1993·Science·D J RawlingsN G Copeland
Jan 21, 1993·Nature·D VetrieM Bobrow
Jan 29, 1993·Cell·S TsukadaS Quan
Dec 15, 1995·Cell·K M FergusonP B Sigler
Jan 1, 1996·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·G Shaw
Jan 1, 1996·Nucleic Acids Research·M VihinenC I Smith
Feb 9, 1996·Science·D J RawlingsJ P Kinet
May 1, 1996·Immunity·H ParkO N Witte
Aug 2, 1996·The Journal of Biological Chemistry·M Fukuda, K Mikoshiba
Citations
May 29, 1999·Journal of Neuroscience Research·A P SignoreH H Yeh
Apr 29, 1999·Human Mutation·M VihinenC I Smith
Jul 1, 1997·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·M Fukuda, K Mikoshiba
Nov 5, 1999·Biochemical and Biophysical Research Communications·M P Okoh, M Vihinen
Oct 12, 2001·Biochemical and Biophysical Research Communications·T MinagawaK Mikoshiba
Jun 10, 1998·Springer Seminars in Immunopathology·C I SmithM Vihinen
Jun 17, 1999·Molecular Neurobiology·H LeVine
Dec 5, 1998·Biochimica Et Biophysica Acta·M J BottomleyG Panayotou
Dec 5, 1998·Biochimica Et Biophysica Acta·P J Cullen
Nov 15, 2002·Molecular Immunology·K M CoggeshallHyewon Phee
Dec 31, 1998·Immunology Letters·R SetoguchiK Takatsu
Feb 27, 1999·Cellular Signalling·K YoshimuraM Hirata
Apr 26, 2002·Current Opinion in Immunology·Andrew T Miller, Leslie J Berg
Jun 1, 1997·Current Opinion in Immunology·A Tarakhovsky
Aug 1, 1997·Current Opinion in Immunology·S Desiderio
Sep 2, 1998·Current Opinion in Immunology·M E Conley, M D Cooper
Jun 1, 1997·Trends in Cell Biology·L M AF K
Nov 5, 1999·Trends in Biochemical Sciences·N BlombergM Saraste
Sep 13, 2000·Molecular Cell·S E LietzkeD G Lambright
Jan 27, 2000·Cytokine & Growth Factor Reviews·H Mano
Jun 19, 2010·Nature Chemical Biology·Tatiana G Kutateladze
Apr 10, 2007·Nature Immunology·Andrew T MillerMichael P Cooke
Mar 26, 2010·Nature Reviews. Immunology·Karsten Sauer, Michael P Cooke
Jan 25, 2008·Nature Reviews. Molecular Cell Biology·Mark A Lemmon
Aug 5, 1999·The Biochemical Journal·J M PasquetS P Watson
Jun 22, 2000·The Biochemical Journal·G CozierP J Cullen
Aug 6, 2000·The Biochemical Journal·M A Lemmon, K M Ferguson
Dec 12, 2001·The Biochemical Journal·Y XuW Hong
Oct 3, 1999·European Journal of Biochemistry·R StrickerG Reiser
May 23, 1998·The Journal of Experimental Medicine·D HataT Kawakami
Nov 24, 1999·The Journal of Experimental Medicine·C L SommersP E Love
Jan 4, 2001·The Journal of Experimental Medicine·D CoxS Greenberg
Aug 7, 1998·Molecular Biology of the Cell·W NagelW Kolanus
Oct 16, 2004·Molecular Biology of the Cell·Susan LeeRichard A Firtel
Jun 1, 1997·The EMBO Journal·M Hyvönen, M Saraste
Sep 16, 1998·The EMBO Journal·G M DingjanR W Hendriks
Sep 16, 1998·The EMBO Journal·S J IsakoffE Y Skolnik
Jun 6, 1998·The EMBO Journal·A M ScharenbergJ P Kinet
Jun 6, 1998·The EMBO Journal·A C FluckigerD J Rawlings
Jun 4, 2010·Cold Spring Harbor Perspectives in Biology·Amy H AndreottiLeslie J Berg
Sep 1, 2011·Science Signaling·Anutosh ChakrabortySolomon H Snyder
Dec 18, 2003·Science's STKE : Signal Transduction Knowledge Environment·Jonathan P DiNittoDavid G Lambright
Dec 16, 2005·Molecular and Cellular Biology·Xuezhi DaiDemin Wang
Jul 1, 1998·Annual Review of Biophysics and Biomolecular Structure·M J Rebecchi, S Scarlata
Mar 18, 2005·Annual Review of Immunology·Leslie J BergPamela L Schwartzberg
Jun 11, 2011·Blood·Tereza OrmsbyAdelheid Cerwenka
May 13, 2008·Journal of Lipid Research·Ju HeTatiana G Kutateladze
Sep 13, 2011·PLoS Computational Biology·Yvonne Y LiSteven J M Jones
Aug 3, 2001·Journal of Neurochemistry·S SanchezF Wandosell
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·A AugustH Hanafusa