Role of the rasGAP-associated docking protein p62(dok) in negative regulation of B cell receptor-mediated signaling.
Role of the rasGAP-associated docking protein p62(dok) in negative regulation of B cell receptor-mediated signaling.
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DOI：
10.1101/gad.14.1.11
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发表时间：
2000-01
影响因子：
10.5
通讯作者：
Y. Yamanashi;T. Tamura;Toshihide Kanamori;H. Yamane;H. Nariuchi;Tadashi Yamamoto;D. Baltimore
中科院分区：
文献类型：
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作者：
Y. Yamanashi;T. Tamura;Toshihide Kanamori;H. Yamane;H. Nariuchi;Tadashi Yamamoto;D. Baltimore
B细胞受体(BCR)的抗原刺激是免疫反应的中心事件。相反，与免疫球蛋白结合的抗原通过将BCR与抑制性受体FcGammaRIIB交联来负向调节BCR发出的信号。在这里，我们表明，当BCR或BCR与FcGammaRIIB交联时，rasGAP相关蛋白p62(Dok)显著地以Lyn依赖的方式酪氨酸磷酸化。通过同源重组使dok基因失活的研究表明，p62(Dok)在BCR交联后抑制MAP激酶，是FcGammaRIIB介导的细胞增殖负调控所必需的。我们认为，p62(Dok)是许多PTK的下游靶标，在各种信号转导情况下起着负性作用。
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.