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Protein kinase C-alpha is an upstream activator of the I kappa B kinase complex in the TPA signal transduction pathway to NF-kappa B in U2OS cells

机译:蛋白激酶C-α是U2OS细胞中通向NF-κB的TPA信号转导途径中IκB激酶复合物的上游激活剂

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Inactive nuclear factor kappaB (NF-kappaB) complexes are retained in the cytoplasm by binding to inhibitory proteins, such as I kappaB alpha. Various stimuli lead to phosphorylation and subsequent processing of I kappaB alpha in the 26S proteasome and import of the active NF-kappaB transcription factor into the nucleus. In agreement with our previous finding that p90(rsk1) is essential for TPA-induced activation of NF-kappaB in Adenovirus 5E1-transformed Baby Rat Kidney cells, we now report that the MEK/ERK/p90(rsk1) inhibitor U0126 efficiently blocks TPA-induced I kappaB alpha processing in these cells. However, in U2OS cells, the cytokine-inducible I kappaB kinase complex (IKK) is the essential component of the TPA signal transduction pathway. Activation of the Wt complex in response to TPA is mediated by PKC-alpha, since both the PKC inhibitor GF109203 and a catalytically inactive PKC-alpha mutant inhibit activation of endogenous IKK by TPA, but not by tumor necrosis factor-alpha (TNF-alpha). We conclude that IKK is an integrator of TNF-alpha and TPA signal transduction pathways in U2OS cells. (C) 2000 Elsevier Science Inc. All rights reserved. [References: 83]
机译:通过与抑制性蛋白质(例如IκBα)结合,无活性核因子κB(NF-kappaB)复合物保留在细胞质中。各种刺激导致26S蛋白酶体中IκBalpha的磷酸化和后续加工,以及活性NF-κB转录因子导入细胞核。与我们先前的发现p90(rsk1)对于TPA诱导的腺病毒5E1转化的大鼠肾脏细胞中TPA诱导的NF-kappaB激活至关重要,我们现在报道MEK / ERK / p90(rsk1)抑制剂U0126有效地阻断了TPA -诱导的IκBα加工在这些细胞中。但是,在U2OS细胞中,细胞因子诱导型IκB激酶复合物(IKK)是TPA信号转导途径的重要组成部分。由于PKC抑制剂GF109203和催化失活的PKC-alpha突变体均抑制TPA内源性IKK的激活,但不影响肿瘤坏死因子-α(TNF-alpha),因此PKC抑制剂GF109203和催化失活的PKC-alpha突变体均会激活PKC-α来激活Wt复合物。 )。我们得出的结论是,IKK是U2OS细胞中TNF-α和TPA信号转导途径的整合者。 (C)2000 Elsevier Science Inc.保留所有权利。 [参考:83]

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