Phospholipase C-γ2 Couples Bruton's Tyrosine Kinase to the NF-κB Signaling Pathway in B Lymphocytes*

By J. B. Petro, W. Khan. Journal of Biological Chemistry, 2001

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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-κB axis following BCR ligation. Interference with this NF-κB cascade may account for some of the B cell defects reported forplc-γ2 − /− mice, which develop an X-linked immunodeficiency-like phenotype.

Subfields: Cancer Research, Genetics, Immunology

View Paper: https://www.semanticscholar.org/paper/314f1212c702c4482767459b114df128b91422c5

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Citations in the corpus

To be, or not to be: NF-κB is the answer – role of Rel/NF-κB in the regulation of apoptosis (2003, background): “…B-lineage-specific depletion of IKKb or IKKg/NEMO, results in dramatic inhibition of NF-kB stimulation following BCR engagement and increased apoptosis (Petro et al., 2000; Leitges et al., 2001; Petro and Khan, 2001; Tan et al., 2001; Martin et al., 2002; Pasparakis et al., 2002b; Li et al., 2003).”
NF‐κB activation by protein kinase C isoforms and B‐cell function (2003, background): “…in response to BCR engagement, but not in response to activation by 12-O-tetradecanoylphorbol-13-acetate plus ionomycin (Petro et al., 2000; Petro & Khan, 2001; Tan et al., 2001), which directly targets the Ca2+- and diacylglycerol (DAG)-sensitive protein kinase C (PKC) isoforms (such as…”