title: Role of the rasGAP-associated docking protein p62(dok) 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 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.
authors.affiliation: Departments of Oncology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo108-8639, Japan. yamanash@ims.u-tokyo.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Yamanashi
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: T
authors.initials: T
authors.lastname: Kanamori
authors.forename: H
authors.initials: H
authors.lastname: Yamane
authors.forename: H
authors.initials: H
authors.lastname: Nariuchi
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: D
authors.initials: D
authors.lastname: Baltimore
mesh_terms: 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
chemical_list: 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