Phospholipase C-γ2 couples Bruton's tyrosine kinase to the NF-κB signaling pathway in B lymphocytes

J. B. Petro, W. N. Khan

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

Mutations in the gene encoding Bruton's tyrosine kinase (BTK) interfere with B cell proliferation and lead to an X-linked immunodeficiency in mice characterized by reduced B cell numbers. Recent studies have established that BTK transmits signals from the B cell antigen receptor (BCR) to transcription factor NF-κB, which in turn reprograms a set of genes required for normal B cell growth. We now demonstrate that induction of NF-κB via this pathway requires the intermediate action of the -γ2 isoform of phospholipase C (PLC-γ2), a potential phosphorylation substrate of BTK. Specifically, pharmacologic agents that block the action of either PLC-γ2 or its second messengers prevent BCR-induced activation of IκB kinase. Moreover, activation of NF-κB in response to BCR signaling is completely abolished in B cells deficient for PLC-γ2. Taken together, these findings strongly suggest that PLC-γ2 functions as an integral component of the BTK/NF-γB axis following BCR ligation. Interference with this NF-κB cascade may account for some of the B cell defects reported for plc-γ2-/- mice, which develop an X-linked immunodeficiency-like phenotype.

Original languageEnglish (US)
Pages (from-to)1715-1719
Number of pages5
JournalJournal of Biological Chemistry
Volume276
Issue number3
DOIs
StatePublished - Jan 19 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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