The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain.

På svenska

Author

  • Abdalla J Mohamed
  • Liang Yu
  • Carl-Magnus Bäckesjö
  • Leonardo Vargas
  • Rani Faryal
  • Alar Aints
  • Birger Christensson
  • Anna Berglöf
  • Mauno Vihinen
  • Beston F Nore
  • C I Edvard Smith
Show all

Summary, in English

Bruton's agammaglobulinemia tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase important in B-lymphocyte development, differentiation, and signaling. Btk is a member of the Tec family of kinases. Mutations in the Btk gene lead to X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. Activation of Btk triggers a cascade of signaling events that culminates in the generation of calcium mobilization and fluxes, cytoskeletal rearrangements, and transcriptional regulation involving nuclear factor-kappaB (NF-kappaB) and nuclear factor of activated T cells (NFAT). In B cells, NF-kappaB was shown to bind to the Btk promoter and induce transcription, whereas the B-cell receptor-dependent NF-kappaB signaling pathway requires functional Btk. Moreover, Btk activation is tightly regulated by a plethora of other signaling proteins including protein kinase C (PKC), Sab/SH3BP5, and caveolin-1. For example, the prolyl isomerase Pin1 negatively regulates Btk by decreasing tyrosine phosphorylation and steady state levels of Btk. It is intriguing that PKC and Pin1, both of which are negative regulators, bind to the pleckstrin homology domain of Btk. To this end, we describe here novel mutations in the pleckstrin homology domain investigated for their transforming capacity. In particular, we show that the mutant D43R behaves similar to E41K, already known to possess such activity.

Publishing year

2009

Language

English

Pages

58-73

Publication/Series

Immunological Reviews

Volume

228

Issue

1

Document type

Journal article review

Publisher

Wiley-Blackwell

Topic

  • Immunology in the medical area

Keywords

  • Agammaglobulinemia: immunology
  • Neoplasms: metabolism
  • Protein-Tyrosine Kinases: chemistry
  • Protein-Tyrosine Kinases: immunology
  • Protein-Tyrosine Kinases: metabolism
  • X-Linked Combined Immunodeficiency Diseases: immunology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1600-065X