Bruton's tyrosine kinase is required for activation of IκB kinase and nuclear factor κB in response to B cell receptor engagement

James B. Petro, S. M Jamshedur Rahman, Dean W. Ballard, Wasif Khan

Research output: Contribution to journalArticle

231 Citations (Scopus)

Abstract

Mutations in the gene encoding Bruton's tyrosine kinase (btk) cause the B cell deficiency diseases X-linked agammaglobulinemia (XLA) in humans and X- linked immunodeficiency (xid) in mice. In vivo and in vitro studies indicate that the BTK protein is essential for B cell survival, cell cycle progression, and proliferation in response to B cell antigen receptor (BCR) stimulation. BCR stimulation leads to the activation of transcription factor nuclear factor (NF)-κB, which in turn regulates genes controlling B cell growth. We now demonstrate that a null mutation in btk known to cause the xid phenotype prevents BCR-induced activation of NF-κB. This defect can be rescued by reconstitution with wild-type BTK. This mutation also interferes with BCR-directed activation of IκB kinase (IKK), which normally targets the NF-κB inhibitor IκBα for degradation. Taken together, these findings indicate that BTK couples IKK and NF-κB to the BCR. Interference with this coupling mechanism may contribute to the B cell deficiencies observed in XLA and xid.

Original languageEnglish
Pages (from-to)1745-1753
Number of pages9
JournalJournal of Experimental Medicine
Volume191
Issue number10
DOIs
StatePublished - May 15 2000
Externally publishedYes

Fingerprint

B-Cell Antigen Receptors
B-Lymphocytes
Phosphotransferases
Mutation
Deficiency Diseases
Genes
Cell Survival
Cell Cycle
Transcription Factors
Cell Proliferation
Agammaglobulinaemia tyrosine kinase
Phenotype
Growth
Proteins

Keywords

  • Antigen receptor signaling
  • Tec family tyrosine kinase
  • Transcription factor
  • X-linked agammaglobulinemia
  • X-linked immunodeficiency

ASJC Scopus subject areas

  • Immunology

Cite this

Bruton's tyrosine kinase is required for activation of IκB kinase and nuclear factor κB in response to B cell receptor engagement. / Petro, James B.; Rahman, S. M Jamshedur; Ballard, Dean W.; Khan, Wasif.

In: Journal of Experimental Medicine, Vol. 191, No. 10, 15.05.2000, p. 1745-1753.

Research output: Contribution to journalArticle

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