Missense mutations affecting a conserved cysteine pair in the TH domain of Btk

FEBS Letters

Koutaniemi, Sanna¹  Watanabe, Chiaki²  Ochs, Hans D.²  Nars, Martin¹  Nore, Beston F.⁵  Vihinen, Mauno³  Mattsson, Pekka T.⁵  Smith, C.I.Edvard⁵  Jones, Allison⁴  Lester, Tracy⁴  Bäckesjö, Carl-Magnus⁵ 

[1] Department of Biochemistry and Food Chemistry, University of Turku, Vatselankatu 2, Arcanum, FIN-20014 Turku, Finland;Department of Pediatrics, University of Washington, Seattle, WA 98195, USA;Department of Biosciences, Division of Biochemistry, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland;Unit of Clinical Genetics, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK;Center for BioTechnology, Department of Biosciences at Novum, Karolinska Institute, S-141 57 Huddinge, Sweden

关键词: Btk;    Bruton's tyrosine kinase;    Signal transduction;    Cytoplasmic tyrosine kinase;    XLA;    X-linked agammaglobulinemia;    Ras GAP;    Btk;    Bruton's tyrosine kinase;    GAP;    GTPase activating protein;    PH;    pleckstrin homology;    PRR;    proline-rich region;    PTK;    protein tyrosine kinase;    SH;    Src homology;    TH;    Tec homology;    XLA;    X-linked agammaglobulinemia;   

DOI  :  10.1016/S0014-5793(97)00912-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Tec family protein tyrosine kinases have in their N-terminus two domains. The PH domain is followed by Tec homology (TH) domain, which consists of two motifs. The first pattern, Btk motif, is also present in some Ras GAP molecules. C-terminal half of the TH domain, a proline-rich region, has been shown to bind to SH3 domains. Mutations in Bruton's tyrosine kinase (Btk) belonging to the Tec family cause X-linked agammaglobulinemia (XLA) due to developmental arrest of B cells. Here we present the first missense mutations in the TH domain. The substitutions affect a conserved pair of cysteines, residues 154 and 155, involved in Zn²⁺ binding and thereby the mutations alter protein folding and stability.

【 授权许可】

Unknown