[HTML][HTML] Bcl10 is a positive regulator of antigen receptor–induced activation of NF-κ B and neural tube closure

J Ruland, GS Duncan, A Elia, I del Barco Barrantes… - Cell, 2001 - cell.com
J Ruland, GS Duncan, A Elia, I del Barco Barrantes, L Nguyen, S Plyte, DG Millar
Cell, 2001cell.com
Bcl10, a CARD-containing protein identified from the t (1; 14)(p22; q32) breakpoint in MALT
lymphomas, has been shown to induce apoptosis and activate NF-κ B in vitro. We show that
one-third of bcl10−/− embryos developed exencephaly, leading to embryonic lethality.
Surprisingly, bcl10−/− cells retained susceptibility to various apoptotic stimuli in vivo and in
vitro. However, surviving bcl10−/− mice were severely immunodeficient and bcl10−/−
lymphocytes are defective in antigen receptor or PMA/Ionomycin-induced activation. Early …
Abstract
Bcl10, a CARD-containing protein identified from the t(1;14)(p22;q32) breakpoint in MALT lymphomas, has been shown to induce apoptosis and activate NF-κ B in vitro. We show that one-third of bcl10−/− embryos developed exencephaly, leading to embryonic lethality. Surprisingly, bcl10−/− cells retained susceptibility to various apoptotic stimuli in vivo and in vitro. However, surviving bcl10−/− mice were severely immunodeficient and bcl10−/− lymphocytes are defective in antigen receptor or PMA/Ionomycin-induced activation. Early tyrosine phosphorylation, MAPK and AP-1 activation, and Ca2+ signaling were normal in mutant lymphocytes, but antigen receptor–induced NF-κ B activation was absent. Thus, Bcl10 functions as a positive regulator of lymphocyte proliferation that specifically connects antigen receptor signaling in B and T cells to NF-κ B activation.
cell.com