NOTCH2 激活及向细胞核传递信号
中文名称
通路描述
与 NOTCH1 类似，NOTCH2 由位于相邻细胞上的 Delta-like 和 Jagged 配体（DLL/JAG）激活（Shimizu et al. 1999, Shimizu et al. 2000, Hicks et al. 2000, Ji et al. 2004）。激活触发 NOTCH2 的切割，首先由 ADAM10 在 S2 切割位点（Gibb et al. 2010, Shimizu et al. 2000）进行切割，然后由 gamma-secretase 在 S3 切割位点（Saxena et al. 2001, De Strooper et al. 1999）进行切割，导致 NOTCH2 的细胞内域 NICD2 释放到细胞质中。NICD2 随后转运至细胞核，作为转录调节因子发挥作用。尽管 DLL 和 JAG 配体已得到证实，但关于 NOTCH2 是否像 NOTCH1 一样由 CNTN1（接触蛋白 1）激活的证据有限，CNTN1 是一种参与寡毛细胞成熟的重要蛋白（Hu et al. 2003）。MDK（中链生长因子），在上皮 - 间质转化中发挥重要作用，也能激活 NOTCH2 信号，并能与 NOTCH2 的细胞外域结合，但 MDK 诱导 NOTCH2 激活的确切机制尚未阐明（Huang et al. 2008, Gungor et al. 2011）。
英文描述
NOTCH2 Activation and Transmission of Signal to the Nucleus Similar to NOTCH1, NOTCH2 is activated by Delta-like and Jagged ligands (DLL/JAG) expressed in trans on a neighboring cell (Shimizu et al. 1999, Shimizu et al. 2000, Hicks et al. 2000, Ji et al. 2004). The activation triggers cleavage of NOTCH2, first by ADAM10 at the S2 cleavage site (Gibb et al. 2010, Shimizu et al. 2000), then by gamma-secretase at the S3 cleavage site (Saxena et al. 2001, De Strooper et al. 1999), resulting in the release of the intracellular domain of NOTCH2, NICD2, into the cytosol. NICD2 subsequently traffics to the nucleus where it acts as a transcription regulator.
While DLL and JAG ligands are well established, canonical NOTCH2 ligands, there is limited evidence that NOTCH2, similar to NOTCH1, can be activated by CNTN1 (contactin 1), a protein involved in oligodendrocyte maturation (Hu et al. 2003). MDK (midkine), which plays an important role in epithelial to mesenchymal transition, can also activate NOTCH2 signaling and is able to bind to the extracellular domain of NOTCH2, but the exact mechanism of MDK-induced NOTCH2 activation has not been elucidated (Huang et al. 2008, Gungor et al. 2011).
While DLL and JAG ligands are well established, canonical NOTCH2 ligands, there is limited evidence that NOTCH2, similar to NOTCH1, can be activated by CNTN1 (contactin 1), a protein involved in oligodendrocyte maturation (Hu et al. 2003). MDK (midkine), which plays an important role in epithelial to mesenchymal transition, can also activate NOTCH2 signaling and is able to bind to the extracellular domain of NOTCH2, but the exact mechanism of MDK-induced NOTCH2 activation has not been elucidated (Huang et al. 2008, Gungor et al. 2011).
所含基因
28 个基因