Rac-mediated stimulation of phospholipase Cγ2 amplifies B cell receptor-induced calcium signaling

Claudia Walliser, Kyrylo Tron, Karen Clauss, Orit Gutman, Andrei Yu Kobitski, Michael Retlich, Anja Schade, Carlheinz Röcker, Yoav I. Henis, G. Ulrich Nienhaus, Peter Gierschik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The Rho GTPase Rac is crucially involved in controlling multiple B cell functions, including those regulated by the B cell receptor (BCR) through increased cytosolic Ca2+. The underlying molecular mechanisms and their relevance to the functions of intact B cells have thus far remained unknown. We have previously shown that the activity of phospholipase Cγ2 (PLCγ2), a key constituent of the BCR signalosome, is stimulated by activated Rac through direct protein-protein interaction. Here, we use a Rac-resistant mutant of PLCγ2 to functionally reconstitute cultured PLCγ2-deficient DT40 B cells and to examine the effects of the Rac-PLCγ2 interaction on BCR-mediated changes of intracellular Ca2+ and regulation of Ca2+-regulated and nuclear-factor-of-activated-T-cell-regulated gene transcription at the level of single, intact B cells. The results show that the functional Rac-PLCγ2 interaction causes marked increases in the following: (i) sensitivity of B cells to BCR ligation; (ii) BCR-mediated Ca2+ release from intracellular stores; (iii) Ca2+ entry from the extracellular compartment; and (iv) nuclear translocation of the Ca2+-regulated nuclear factor of activated T cells. Hence, Rac-mediated stimulation of PLCγ2 activity serves to amplify B cell receptor-induced Ca2+ signaling.

Original languageEnglish
Pages (from-to)17056-17072
Number of pages17
JournalJournal of Biological Chemistry
Issue number28
StatePublished - 10 Jul 2015


FundersFunder number
Deutsche ForschungsgemeinschaftSFB 1074, SFB 497


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