高级糖基化终产物受体信号传导
中文名称
通路描述
高级糖基化终产物受体（AGER），也称为高级糖基化终产物受体（RAGE），是一种属于免疫球蛋白超家族的多种配体膜受体。它被认为是模式识别受体（Liliensiek 等，2004）。它识别各种已修饰的蛋白质，称为高级糖基化/糖基化终产物（AGEs），这是一种由马利兰反应生成、蛋白质与葡萄糖长期孵化的异构结构群（Ikeda 等，1996）。它们的积累与糖尿病、动脉粥样硬化、肾衰竭和衰老相关（Schmidt 等，1999）。体内最普遍的 AGE 类是 N(6)-羧甲基赖氨酸（NECML）加合物（Kislinger 等，1991）。除了 AGEs 外，AGER 也是淀粉样 beta 肽（Ab）的信号转导受体（Yan 等，1996），介导 Ab 神经毒性并促进 Ab 进入大脑。AGER 还响应促炎 S100/钙调蛋白（Hofmann 等，1999）和高迁移率组蛋白 B1（HMGB1/Amphoterin/DEF），这是一种与轴突生长和细胞运动相关的蛋白质（Hori 等，1995）。AGER 激活的主要炎症通路是 NF-kappaB。尽管信号级联尚不清楚，但几项实验数据表明，AGER 的激活导致 NF-kappaB 的持续激活和上调，以 NF-kappaB 转位到细胞核和新生 NF-kappaB 水平增加为测量指标（Bierhaus 等，2001）。由于这显然是间接效应，这里将其表示为 NF-kappaB 转位到细胞核的正向调节。AGER 可与 ERK1/2 结合，从而激活 MAPK 和 JNK 级联（Bierhaus 等，2005）。
英文描述
Advanced glycosylation endproduct receptor signaling Advanced Glycosylation End- product-specific Receptor (AGER) also known as Receptor for Advanced Glycation End-products (RAGE) is a multi-ligand membrane receptor belonging to the immunoglobulin superfamily. It is considered to be a Pattern Recognition Receptor (Liliensiek et al. 2004). It recognizes a large variety of modified proteins known as advanced glycation/glycosylation endproducts (AGEs), a heterogenous group of structures that are generated by the Maillard reaction, a consequence of long-term incubation of proteins with glucose (Ikeda et al. 1996). Their accumulation is associated with diabetes, atherosclerosis, renal failure and ageing (Schmidt et al. 1999). The most prevalent class of AGE in vivo are N(6)-carboxymethyllysine (NECML) adducts (Kislinger et al. 1991). In addition to AGEs, AGER is a signal transduction receptor for amyloid-beta peptide (Ab) (Yan et al. 1996), mediating Ab neurotoxicity and promoting Ab influx into the brain. AGER also responds to the proinflammatory S100/calgranulins (Hofmann et al. 1999) and High mobility group protein B1 (HMGB1/Amphoterin/DEF), a protein linked to neurite outgrowth and cellular motility (Hori et al. 1995).
The major inflammatory pathway stimulated by AGER activation is NFkappaB. Though the signaling cascade is unclear, several pieces of experimental data suggest that activation of AGER leads to sustained activation and upregulation of NFkappaB, measured as NFkappaB translocation to the nucleus, and increased levels of de novo synthesized NFkappaB (Bierhaus et al. 2001). As this is clearly an indirect effect it is represented here as positive regulation of NFkappaB translocation to the nucleus. AGER can bind ERK1/2 and thereby activate the MAPK and JNK cascades (Bierhaus et al. 2005).
The major inflammatory pathway stimulated by AGER activation is NFkappaB. Though the signaling cascade is unclear, several pieces of experimental data suggest that activation of AGER leads to sustained activation and upregulation of NFkappaB, measured as NFkappaB translocation to the nucleus, and increased levels of de novo synthesized NFkappaB (Bierhaus et al. 2001). As this is clearly an indirect effect it is represented here as positive regulation of NFkappaB translocation to the nucleus. AGER can bind ERK1/2 and thereby activate the MAPK and JNK cascades (Bierhaus et al. 2005).
所含基因
13 个基因