PKC-β controls IκB kinase lipid raft recruitment and activation in response to BCR signaling
PKC-β controls IκB kinase lipid raft recruitment and activation in response to BCR signaling
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DOI：
10.1038/ni823
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发表时间：
2002-08-01
影响因子：
30.5
通讯作者：
Rawlings, DJ
中科院分区：
文献类型：
--
作者：
Su, TT;Guo, BC;Rawlings, DJ
核因子-kappaB信号是维持正常B淋巴细胞所必需的，而失调的核因子-kappaB活化参与了B细胞淋巴瘤的发生。调节B淋巴细胞中的核因子-kappaB信号的事件还不清楚。在这里，我们证明了PKC-β是B细胞受体(BCR)介导的NF-kappaB激活所必需的。来自蛋白激酶C-β(PKC-beta)缺陷小鼠的B细胞未能将IkappaB激酶(IKK)复合体招募到脂筏中，激活IKK，降解IkappaB，或上调依赖于NF-kappaB的生存信号。抑制PKC-β促进了B淋巴瘤的细胞死亡，其特征是核因子-kappaB活性被夸大。总之，这些数据定义了PKC-β在bcr生存信号中的重要作用，并强调了PKC-beta是B系恶性肿瘤的关键治疗靶点。
NF-kappaB signaling is required for the maintenance of normal B lymphocytes, whereas dysregulated NF-kappaB activation contributes to B cell lymphomas. The events that regulate NF-kappaB signaling in B lymphocytes are poorly defined. Here, we demonstrate that PKC-beta is specifically required for B cell receptor (BCR)-mediated NF-kappaB activation. B cells from protein kinase C-beta (PKC-beta)-deficient mice failed to recruit the IkappaB kinase (IKK) complex into lipid rafts, activate IKK, degrade IkappaB or up-regulate NF-kappaB-dependent survival signals. Inhibition of PKC-beta promoted cell death in B lymphomas characterized by exaggerated NF-kappaB activity. Together, these data define an essential role for PKC-beta in BCR survival signaling and highlight PKC-beta as a key therapeutic target for B-lineage malignancies.