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Genes & Dev. 14 (1): 11-16

Copyright © 2000 by Cold Spring Harbor Laboratory Press.

Vol. 14, No. 1, pp. 11-16, January 1, 2000

RESEARCH COMMUNICATION
Role of the rasGAP-associated docking protein p62dok in negative regulation of B cell receptor-mediated signaling

Yuji Yamanashi,1,2 Toshiki Tamura,3 Toshihide Kanamori,1 Hidehiro Yamane,3 Hideo Nariuchi,3 Tadashi Yamamoto,1 and David Baltimore4

1 Departments of Oncology and 3 Allergology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo108-8639, Japan; 4 California Institute of Technology, Pasadena, California 91125 USA

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 Fcgamma RIIB. Here we show that upon cross-linking of BCR or BCR with Fcgamma RIIB, the rasGAP-associated protein p62dok is prominently tyrosine phosphorylated in a Lyn-dependent manner. Inactivation of the dok gene by homologous recombination has shown that upon BCR cross-linking, p62dok suppresses MAP kinase and is indispensable for Fcgamma RIIB-mediated negative regulation of cell proliferation. We propose that p62dok, a downstream target of many PTKs, plays a negative role in various signaling situations.

[Key Words: Dok; Lyn; B cell receptor; Fcgamma RIIB; tyrosine kinase; MAP kinase]

2 Corresponding author.

GENES & DEVELOPMENT 14:11-16 © 2000 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/00 $5.00

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