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论文题目: A negative-feedback function of PKC beta in the formation and accumulation of signaling-active B cell receptor microclusters within B cell immunological synapse
英文论文题目: A negative-feedback function of PKC beta in the formation and accumulation of signaling-active B cell receptor microclusters within B cell immunological synapse
第一作者: Liu, C; Zhao, XW; Xu, LL; Yi, JY; Shaheen, S; Han, WD; Wang, F; Zheng, WJ; Xu, CQ; Liu, WL
英文第一作者: Liu, C; Zhao, XW; Xu, LL; Yi, JY; Shaheen, S; Han, WD; Wang, F; Zheng, WJ; Xu, CQ; Liu, WL
联系作者: Liu, WL (reprint author), Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
英文联系作者: Liu, WL (reprint author), Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
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发表年度: 2015
卷: 97
期: 5
页码: 887-900
摘要: Advanced live cell imaging studies suggested that B cell activation is initiated by the formation of BCR microclusters and subsequent B cell IS upon BCR and antigen recognition. PKC family member PKC beta is highly expressed in B cells and plays an important role in the initiation of B cell activation. Here, we reported an inhibitory function of PKC beta through a negative-feedback manner in B cell activation. Compared with WT (PKC beta-WT) or the constitutively active (PKC beta-DNPS) form of PKC beta, DN PKC beta (PKC beta-DN) unexpectedly enhanced the accumulation of BCR microclusters into the B cell IS, leading to the recruitment of an excessive amount of pSyk, pPLC-gamma 2, and pBLNK signaling molecules into the membrane-proximal BCR signalosome. Enhanced calcium mobilization responses in the decay phase were also observed in B cells expressing PKC beta-DN. Mechanistic studies showed that this negative-feedback function of PKC beta works through the induction of an inhibitory form of pBtk at S180 (pBtk-S180). Indeed, the capability of inducing the formation of an inhibitory pBtk-S180 is in the order of PKC beta-DNPS. PKC beta-WT. PKC beta-DN. Thus, these results improve our comprehensive understanding on the positive and negative function of PKC beta in the fine tune of B cell activation.
英文摘要: Advanced live cell imaging studies suggested that B cell activation is initiated by the formation of BCR microclusters and subsequent B cell IS upon BCR and antigen recognition. PKC family member PKC beta is highly expressed in B cells and plays an important role in the initiation of B cell activation. Here, we reported an inhibitory function of PKC beta through a negative-feedback manner in B cell activation. Compared with WT (PKC beta-WT) or the constitutively active (PKC beta-DNPS) form of PKC beta, DN PKC beta (PKC beta-DN) unexpectedly enhanced the accumulation of BCR microclusters into the B cell IS, leading to the recruitment of an excessive amount of pSyk, pPLC-gamma 2, and pBLNK signaling molecules into the membrane-proximal BCR signalosome. Enhanced calcium mobilization responses in the decay phase were also observed in B cells expressing PKC beta-DN. Mechanistic studies showed that this negative-feedback function of PKC beta works through the induction of an inhibitory form of pBtk at S180 (pBtk-S180). Indeed, the capability of inducing the formation of an inhibitory pBtk-S180 is in the order of PKC beta-DNPS. PKC beta-WT. PKC beta-DN. Thus, these results improve our comprehensive understanding on the positive and negative function of PKC beta in the fine tune of B cell activation.
刊物名称: JOURNAL OF LEUKOCYTE BIOLOGY
英文刊物名称: JOURNAL OF LEUKOCYTE BIOLOGY
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学科: Cell Biology; Hematology; Immunology
英文学科: Cell Biology; Hematology; Immunology
影响因子: 4.289
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论文类别: Article
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