Figure 7.

Inhibition of BCR-induced Ca²⁺ signaling by the Dok-3/Grb2 module. The Dok-3 adaptor protein is tethered at the inner side of the plasma membrane by virtue of its PH domain. Following tyrosine phosphorylation in activated B cells, Dok-3 recruits Grb2, which at this specific subcellular location attenuates Btk-dependent activation of PLC-γ2 by interfering with the proper formation of the SLP-65-assembled Ca²⁺ initiation complex and/or inhibiting the enzymatic activity of Btk. Positive and negative regulators of Ca²⁺ elevation are illustrated by open and filled boxes, respectively. The BCR complex is depicted in gray.