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

Yamanashi Y., Tamura T., Kanamori T., Yamane H., Nariuchi H., Yamamoto T., Baltimore D.

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 FcgammaRIIB. Here we show that upon cross-linking of BCR or BCR with FcgammaRIIB, 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 FcgammaRIIB-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.

Genes Dev. 14:11-16(2000) [PubMed] [Europe PMC]