Role of the rasGAP-associated docking protein p62 dok in negative regulation of B cell receptor-mediated signaling

Antigenic stimulation of the B-cell receptor (BCR) is a central event in the immune response. In contrast, antigen bound to IgG negatively regulates signals from the BCR by cross-linking it to the inhibitory receptor FcγRIIB. Here we show that upon cross-linking of BCR or BCR with FcγRIIB, the rasGAP-associated protein p62 dok is prominently tyrosine phosphorylated in a Lyn-dependent manner. Inactivation of the dok gene by homologous recombination has shown that upon BCR cross-linking, p62 dok suppresses MAP kinase and is indispensable for FcγRIIB-mediated negative regulation of cell proliferation. We propose that p62 dok , a downstream target of many PTKs, plays a negative role in various signaling situations.