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 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.
Yamanashi
Y
Y
Departments of Oncology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo108-8639, Japan. yamanash@ims.u-tokyo.ac.jp
Tamura
T
T
Kanamori
T
T
Yamane
H
H
Nariuchi
H
H
Yamamoto
T
T
Baltimore
D
D
D000818:Animals; D004268:DNA-Binding Proteins; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D016601:RNA-Binding Proteins; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; C489561:Dok1 protein, mouse; C074561:GAP-associated protein p62; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D014443:Tyrosine