NOTCH4 激活及信号向细胞核传递
中文名称
通路描述
NOTCH4 与 DLL4（Delta-4）和 JAG1（Jagged-1）在血管系统中共表达（Shutter et al. 2000, Uyttendaele et al. 2000）。当 HMVECd 细胞（人原代内皮细胞系，源自新生儿微血管）或 HUVEC 细胞（人脐静脉内皮细胞系）与表达重组小鼠 Notch4 的细胞共培养时，NOTCH4 可被 DLL4 和 JAG1 激活（Shawber et al. 2003, Shawber et al. 2007）。当使用 Notch4-或 Dll4-或 Jag1-表达载体转导小鼠成纤维细胞系 NIH 3T3 或人胚胎肾细胞系 HEK293 进行共培养实验时，NOTCH4 由 DLL4 和 JAG1 激活的现象无法重现（Aste-Amezaga et al. 2010, James et al. 2014）。NOTCH4 的信号传递类似于其他 NOTCH 家族蛋白，涉及膜结合型 NOTCH4 受体的蛋白酶解，释放入胞质的 NOTCH4 胞内片段（NICD4）（Saxena et al. 2001, Das et al. 2004）。NICD4 从胞质转运至细胞核，在那里作为转录因子发挥作用（Lin et al. 2002）。
英文描述
Formation of ATP by chemiosmotic coupling The re-entry of protons into the mitochondrial matrix through Complex V causes conformational changes which result in ATP synthesis. Complex V (ATP synthase) is composed of 3 parts; an F1 catalytic core (approx 5 subunits), an F0 membrane proton channel (approx 9 subunits) and two stalks linking F1 to F0. F1 contains three alpha subunits, three beta subunits, and one each of gamma, delta, and epsilon subunits. Each beta subunit contains an active site for ATP synthesis. F0 has at least 9 subunits (a-g, A6L and F6; see Lai et al., 2023; reviewed in Jonckheere et al., 2011).
The mechanism of ATP synthesis by Complex V was predicted by Boyer et al in 1973: ADP and Pi bind to the enzyme resulting in a conformational change. ATP is then synthesized, still bound to the enzyme. Another change in the active site results in the release of free ATP into the matrix. The overall reaction is:
ADP + Pi + H+ + nH+ (intermemb. space) = ATP + H2O + nH+ (matrix)
Mutations in several ATP synthase subunits can lead to different types of mitochondrial complex V deficiency (MC5D; reviewed in Garone et al., 2022; Del Dotto et al., 2024).
The mechanism of ATP synthesis by Complex V was predicted by Boyer et al in 1973: ADP and Pi bind to the enzyme resulting in a conformational change. ATP is then synthesized, still bound to the enzyme. Another change in the active site results in the release of free ATP into the matrix. The overall reaction is:
ADP + Pi + H+ + nH+ (intermemb. space) = ATP + H2O + nH+ (matrix)
Mutations in several ATP synthase subunits can lead to different types of mitochondrial complex V deficiency (MC5D; reviewed in Garone et al., 2022; Del Dotto et al., 2024).
所含基因
19 个基因