PI5P, PP2A 和 IER3 调节 PI3K/AKT 信号通路
中文名称
通路描述
磷脂酰肌醇-5-磷酸（PI5P）可能通过多种方式调节 PI3K/AKT 信号通路。PI5P 是磷脂酰肌醇-4,5-双磷酸（PI(4,5)P2）的前体，而 PI(4,5)P2 是 PI3K 的底物，进而产生 PIP3。然而，细胞内大部分的 PI(4,5)P2 来自磷脂酰肌醇-4-磷酸（PI4P）底物。PIP3 对于 AKT 的激活磷酸化是必需的。AKT1 可通过含有调节亚基 B56-beta（PPP2R5B）或 B56-gamma（PPP2R5C）的蛋白磷酸酶 2A（PP2A）复合物被去磷酸化。PI5P 通过未知机制抑制 PP2A 对 AKT1 的去磷酸化，增加 PI5P 水平与 PP2A 复合物的抑制性磷酸化相关。MAPK1（ERK2）和 MAPK3（ERK1）参与通过 IER3（IEX-1）抑制 PP2A 的磷酸化过程。然而，尚不清楚 PI5P 是否参与 ERK 介导的 PP2A 磷酸化，或者是否调节另一种 PP2A 激酶。
英文描述
Degradation of GLI1 by the proteasome GLI1 is the most divergent of the 3 mammalian GLI transcription factors and lacks a transcriptional repressor domain. Although GLI1 is dispensible for development, the gene is an early transcriptional target of Hh signaling and the protein contributes a minor activation function in mammals (Dai et al, 1999; Bai et al, 2002; Park et al, 2000).
In the absence of Hh signaling, GLI1 is completely degraded by the proteasome, in contrast to the partial processing that occurs with GLI3. This differential response reflects the absence in GLI1 of two of the three elements identified in GLI3 that promote partial proteolysis; these are the zinc finger region, present in all GLI proteins, and an adjacent linker sequence and the degron, neither of which are found in the GLI1 protein (Schrader et al, 2011; Pan and Wang, 2007).
In the absence of Hh signaling, GLI1 is completely degraded by the proteasome, in contrast to the partial processing that occurs with GLI3. This differential response reflects the absence in GLI1 of two of the three elements identified in GLI3 that promote partial proteolysis; these are the zinc finger region, present in all GLI proteins, and an adjacent linker sequence and the degron, neither of which are found in the GLI1 protein (Schrader et al, 2011; Pan and Wang, 2007).
所含基因
47 个基因