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A novel calmodulin-β-PIX interaction and its implication in receptor tyrosine kinase regulation

机译:钙调蛋白-β-PIX的新型相互作用及其在受体酪氨酸激酶调节中的意义

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摘要

Calmodulin (CaM), a ubiquitous calcium-binding protein, regulates numerous cellular processes, primarily in response to calcium flux. We have identified and characterized a novel interaction between CaM and β-p21-activated kinase interacting exchange factor (β-PIX), a putative guanine exchange factor implicated in cell signaling, using affinity pull-down assays, co-immunoprecipitation, co-localization and circular dichroism studies. Fluorescence-based titration and isothermal titration calorimetry experiments revealed a Ca ~(2+)-dependent binding mechanism (K _D≤10μM). Further, we show that CaM participates in a multi-protein complex involving β-PIX and E3 ubiquitin ligase c-Cbl (casitas B-cell lymphoma), which may play a critical role in receptor tyrosine kinase regulation and downstream signaling.
机译:钙调蛋白(CaM)是一种普遍存在的钙结合蛋白,主要是响应钙通量来调节许多细胞过程。我们已经使用亲和力下拉测定法,共免疫沉淀法,共定位法确定了CaM与β-p21激活的激酶相互作用交换因子(β-PIX)之间的新型相互作用,β-PIX是一种牵涉在细胞信号传导中的鸟嘌呤交换因子。和圆二色性研究。基于荧光的滴定和等温滴定量热法实验揭示了Ca〜(2+)依赖性的结合机理(K_D≤10μM)。此外,我们显示CaM参与了涉及β-PIX和E3泛素连接酶c-Cbl(卡西塔斯B细胞淋巴瘤)的多蛋白复合物,这可能在受体酪氨酸激酶调节和下游信号传导中起关键作用。

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