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首页> 外文期刊>Cellular Signalling >PKCε acts as negative allosteric modulator of EGF receptor signalling
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PKCε acts as negative allosteric modulator of EGF receptor signalling

机译：PKCε充当EGF受体信号转导的负变构调节剂

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Protein kinase C ε (PKCε) is a transforming oncogene and plays a pivotal role in numerous cellular processes including proliferation, invasion and differentiation. Recently, we described a function of PKCε as a scaffold protein linking PLCγ1 to the EGFR module. Here, in the head and neck squamous carcinoma cell line (HNSCC) FaDu we demonstrate that over-expressed PKCε may be associated with the EGFR. This is linked with the consecutive inhibition of the recruitment of PLCγ1 to the EGFR, of the catalytical activation of PLCγ1 by EGF, and of the PLCγ1-mediated effect of EGF on cell proliferation. These effects are independent of the catalytical as well as the scaffold activity of PKCε but are a function of the cellular expression level of PKCε. In contrast to FaDu cells where the PLCγ1 pathway was selectively affected, in three other HNSCC cell lines investigated over-expression of PKCε resulted in association with EGFR and, subsequently, in either partial (ERK and Akt or PLCγ1 and Akt) or complete (ERK, PLCγ1 and Akt) inhibition of the main EGFR signalling pathways. Together, our data suggest that in particular carcinoma cells highly expressed PKCε may act as negative allosteric modulator of EGFR signalling. This novel function of PKCε provides also the first indication that the EGFR may be a target for allosteric modulation by accessory proteins.
机译：蛋白激酶Cε（PKCε）是一种转化癌基因，在众多细胞过程（包括增殖，侵袭和分化）中起着关键作用。最近，我们描述了PKCε作为将PLCγ1连接至EGFR模块的支架蛋白的功能。在这里，在头颈部鳞状细胞癌细胞系（HNSCC）FaDu中，我们证明了过表达的PKCε可能与EGFR有关。这与对PLCγ1募集到EGFR的连续抑制，EGF对PLCγ1的催化活化以及EGF对细胞增殖的PLCγ1介导作用的连续抑制有关。这些作用与PKCε的催化活性和支架活性无关，但与PKCε的细胞表达水平有关。与选择性地影响PLCγ1途径的FaDu细胞相反，在其他三个研究的HNSCC细胞系中，PKCε的过度表达导致与EGFR结合，随后部分或部分（ERK和Akt或PLCγ1和Akt）或全部（ERK） ，PLCγ1和Akt）抑制主要的EGFR信号通路。总之，我们的数据表明，特别是高表达的PKCε癌细胞可能充当EGFR信号的负变构调节剂。 PKCε的这一新功能还首次表明EGFR可能是辅助蛋白进行变构调节的靶标。

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