Mauno Vihinen¹, Pekka T. Mattsson^2,3 and C. I. Edvard Smith²

¹Department of Biosciences, Division of Biochemistry, P. O. Box 56, FIN-00014 University of Helsinki, Finland

²Center for BioTechnology, Department of Bioscience at Novum, Karolinska Institute, S-141 57 Huddinge and Department of Immunology, Microbiology, Pathology and Infectious Diseases (IMPI), Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Sweden

³Department of Biochemistry and Food Chemistry, University of Turku, Vatselankatu 2, Arcanum, FIN-20014 Turku, Finland

Received 11/24/96; Accepted 12/16/96; On-line 01/01/97

1. ABSTRACT

X-linked agammaglobulinemia (XLA) is a heritable immunodeficiency disorder that is caused by a differentiation block leading to almost complete absence of B lymphocytes and plasma cells. The affected protein is a cytoplasmic protein tyrosine kinase, Bruton's agammaglobulinemia tyrosine kinase (Btk). Btk along with Tec, Itk and Bmx belong to a distinct family of protein kinases. These proteins contain five regions; PH, TH, SH3, SH2 and kinase domains. Mutations causing XLA may affect any of these domains. About 200 unique mutations have been identified and are collected in a mutation database, BTKbase. Here, we describle, the structure, function, and interactions of the affected signaling molecules in atomic detail.