Role of the rasGAP-associated docking protein p62dok in negative regulation of B cell receptor-mediated signaling
Abstract
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 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 FcγRIIB-mediated negative regulation of cell proliferation. We propose that p62dok, a downstream target of many PTKs, plays a negative role in various signaling situations.
Keywords
Footnotes
-
↵2 Corresponding author.
-
E-MAIL yamanash{at}ims.u-tokyo.ac.jp; FAX 81-3-5449-5413.
-
- Received September 27, 1999.
- Accepted November 18, 1999.
- Cold Spring Harbor Laboratory Press