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 th e immune response. In contrast, antigen bound to IgG negatively regulates s ignals from the BCR by cross-linking it to the inhibitory receptor Fc gamma RIIB. Here we show that upon cross-linking of BCR or ECR with Fc gamma RII B, the rasGAP-associated protein p62(dok) is prominently tyrosine phosphory lated in a Lyn-dependent manner. Inactivation of the dok gene by homologous recombination has shown that upon BCR cross-linking, p62(dok) suppresses M AP kinase and is indispensable for Fc gamma RIIB-mediated negative regulati on of cell proliferation. We propose that p62(dok), a downstream target of many PTKs, plays a negative role in various signaling situations.