ERBB2:ERBB3信号的下调
中文名称
通路描述
细胞膜上ERBB3的水平由E3泛素连接酶RNF41（也称为NRDP1）调节，该酶结合并泛素化既无活性又激活的ERBB3，将其靶向降解（Cao et al. 2007）。RNF41受自泛素化调节，当ERBB3未受刺激时保持其水平较低，并保留ERBB3在细胞表面（Qiu et al. 2002）。RNF41的自泛素化是可逆的，通过泛素蛋白酶USP8的作用实现，该酶由AKT介导的磷酸化稳定。因此，ERBB2:ERBB3信号激活AKT导致USP8磷酸化（Cao et al. 2007），通过去泛素化增加RNF41的水平，并导致激活的ERBB3降解（Cao et al. 2007）——这是ERBB3信号的一个负反馈回路。EGFR和ERBB4信号的下调在Signaling by EGFR和Signaling by ERBB4途径中解释。
英文描述
Downregulation of ERBB2:ERBB3 signaling Level of plasma membrane ERBB3 is regulated by E3 ubiquitin ligase RNF41 (also known as NRDP1), which binds and ubiquitinates both inactive and activated ERBB3, targeting it for degradation (Cao et al. 2007). RNF41 is subject to self-ubiquitination which keeps its levels low when ERBB3 is not stimulated, and preserves ERBB3 expression on the cell surface (Qiu et al. 2002). Self-ubiquitination of RNF41 is reversible, through the action of ubiquitin protease USP8, an enzyme stabilized by AKT-mediated phosphorylation. Therefore, activation of AKT by ERBB2:ERBB3 signaling leads to phosphorylation of USP8 (Cao et al. 2007), which increases level of RNF41 through deubiquitination, and results in degradation of activated ERBB3 (Cao et al. 2007) - a negative feedback loop of ERBB3 signaling. Downregulation of EGFR and ERBB4 signaling is explained in pathways Signaling by EGFR and Signaling by ERBB4.
所含基因
12 个基因