RKIP regulates MAP kinase signaling in cells with defective B-Raf activity.
RKIP regulates MAP kinase signaling in cells with defective B-Raf activity.
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RKIP 调节 B-Raf 活性缺陷细胞中的 MAP 激酶信号传导。
DOI：
10.1016/j.cellsig.2013.02.005
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发表时间：
2013
影响因子：
4.8
通讯作者：
Rosner,MarshaRich
中科院分区：
文献类型：
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作者：
Zeng,Lingchun;Ehrenreiter,Karin;Menon,Jyotsana;Menard,Ray;Kern,Florian;Nakazawa,Yoko;Bevilacqua,Elena;Imamoto,Akira;Baccarini,Manuela;Rosner,MarshaRich
MAP激酶(MAPK)信号转导是Raf激酶对外界或内部刺激反应激活的结果。在这里，我们证明了当B-Raf信号缺陷时，Raf激酶抑制蛋白(RKIP)调节MAPK的激活。我们使用了多种模型，包括小鼠胚胎成纤维细胞(MEF)和RKIP或Raf缺陷小鼠的原代角质形成细胞，以及小鼠的同种异体移植，以探讨其机制。B-Raf蛋白或活性的丧失显著降低了这些细胞中MAPK的激活。我们发现，RKIP的缺失可以挽救受损的ERK激活并促进其增殖，这种挽救是通过依赖Raf-1的机制发生的。这些结果为RKIP是Raf-1的真正调节者提供了正式证据。我们提出了一个新的模型，在该模型中，RKIP在调节B-Raf受损细胞中通过Raf-1向ERK传递信号的能力方面发挥关键作用。
MAP kinase (MAPK) signaling results from activation of Raf kinases in response to external or internal stimuli. Here, we demonstrate that Raf kinase inhibitory protein (RKIP) regulates the activation of MAPK when B-Raf signaling is defective. We used multiple models including mouse embryonic fibroblasts (MEFs) and primary keratinocytes from RKIP- or Raf-deficient mice as well as allografts in mice to investigate the mechanism. Loss of B-Raf protein or activity significantly reduces MAPK activation in these cells. We show that RKIP depletion can rescue the compromised ERK activation and promote proliferation, and this rescue occurs through a Raf-1 dependent mechanism. These results provide formal evidence that RKIP is a bona fide regulator of Raf-1. We propose a new model in which RKIP plays a key role in regulating the ability of cells to signal through Raf-1 to ERK in B-Raf compromised cells.