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Istituto di scienza dell'alimentazione

Torna all'elenco Contributi in rivista anno 2008

Contributo in rivista

Tipo: Articolo in rivista

Titolo: Physical and functional characterization of the genetic locus of IBtk, an inhibitor of Bruton's tyrosine kinase: evidence for three protein isoforms of IBtk.

Anno di pubblicazione: 2008

Formato: Elettronico Cartaceo

Autori: Spatuzza C; Schiavone M; Di Salle E; Janda E; Sardiello M; Fiume G; Fierro O; Simonetta M; Argiriou N; Faraonio R; Capparelli R; Quinto I; Scala G.

Affiliazioni autori: Spatuzza C. Department of Experimental and Clinical Medicine, University of Catanzaro ‘Magna Graecia’, Catanzaro. Schiavone M. Department of Experimental and Clinical Medicine, University of Catanzaro ‘Magna Graecia’, Catanzaro. Di Salle E. Department of Biochemistry and Medical Biotechnology, University of Naples ‘Federico II’. Janda E. Department of Experimental and Clinical Medicine, University of Catanzaro ‘Magna Graecia’, Catanzaro. Sardiello M. Telethon Institute of Genetics and Medicine, Naples. Fiume G. Department of Experimental and Clinical Medicine, University of Catanzaro ‘Magna Graecia’, Catanzaro. Fierro O. Institute of Food Sciences, CNR, Avellino Simonetta M. Department of Biochemistry and Medical Biotechnology, University of Naples ‘Federico II’. Argiriou N. Department of Biochemistry and Medical Biotechnology, University of Naples ‘Federico II’. Faraonio R. Department of Biochemistry and Medical Biotechnology, University of Naples ‘Federico II’. Capparelli R. Department of Biotechnological Sciences, University of Naples ‘Federico II’, Naples. Quinto I. Department of Experimental and Clinical Medicine, University of Catanzaro ‘Magna Graecia’, Catanzaro. Scala G. Department of Experimental and Clinical Medicine, University of Catanzaro ‘Magna Graecia’, Catanzaro.

Autori CNR:

  • OLGA FIERRO

Lingua: inglese

Abstract: Bruton's tyrosine kinase (Btk) is required for B-cell development. Btk deficiency causes X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. Btk lacks a negative regulatory domain and may rely on cytoplasmic proteins to regulate its activity. Consistently, we identified an inhibitor of Btk, IBtk, which binds to the PH domain of Btk and down-regulates the Btk kinase activity. IBtk is an evolutionary conserved protein encoded by a single genomic sequence at 6q14.1 cytogenetic location, a region of recurrent chromosomal aberrations in lymphoproliferative disorders; however, the physical and functional organization of IBTK is unknown. Here, we report that the human IBTK locus includes three distinct mRNAs arising from complete intron splicing, an additional polyadenylation signal and a second transcription start site that utilizes a specific ATG for protein translation. By northern blot, 5'RACE and 3'RACE we identified three IBTKalpha, IBTKbeta and IBTKgamma mRNAs, whose transcription is driven by two distinct promoter regions; the corresponding IBtk proteins were detected in human cells and mouse tissues by specific antibodies. These results provide the first characterization of the human IBTK locus and may assist in understanding the in vivo function of IBtk.

Lingua abstract: inglese

Pagine da: 4402

Pagine a: 4416

Pagine totali: 14

Rivista:

Nucleic acids research Oxford University Press
Paese di pubblicazione: Regno Unito
Lingua: inglese
ISSN: 0305-1048

Numero volume: 36

DOI: 10.1093/nar/gkn413

Referee: Sì: Internazionale

Indicizzato da: ISI Web of Science (WOS) [000257964500024]

Parole chiave:

  • X-LINKED AGAMMAGLOBULINEMIA
  • PLECKSTRIN HOMOLOGY DOMAINS
  • PRE-B CELLS
  • NF-KAPPA-B
  • TRANSCRIPTIONAL ACTIVITY.

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