RAF/MAP kinase 信号通路
中文名称
通路描述
RAS-RAF-MEK-ERK 通路通过生长因子、激素和细胞因子等刺激，调节细胞的增殖、分化、生存、衰老和细胞运动。这些刺激与细胞膜上的受体结合后，促进膜上 GEF 介导的 RAS 激活，进而启动传统的 MAPK 三级激酶级联反应。GTP 结合的 RAS 招募 RAF（MAPK 激酶激酶），促进其二聚化和激活。活化的 RAF 磷酸化 MAPK 激酶蛋白 MEK1 和 MEK2（即 MAP2K1 和 MAP2K2），后者再磷酸化丝氨酸/苏氨酸导向的激酶 ERK1 和 ERK2（即 MAPK3 和 MAPK1）。活化的 ERK 蛋白可能发生二聚化，并识别细胞核和细胞质中的靶蛋白；正如所见，在刺激下，部分活化的 ERK 蛋白会重新定位到细胞核内。尽管最初被视为从细胞膜开始、最终到达细胞核的线性级联，但 RAS/RAF MAPK 级联现已也被证实可从细胞内各种位置激活。通路组件与多种支架蛋白的相互作用部分实现了该级联的时空特异性。RAS/RAF MAPK 级联的重要性体现在其组件在人类多种癌症中以高频率发生突变的事实。约三分之一的癌症中存在 RAS 激活突变，而约 8% 的肿瘤表达活化的 BRAF 形式。
英文描述
FMO oxidises nucleophiles Flavin-containing monooxygenases (FMOs) are the second family of microsomal oxidative enzymes with broad and overlapping specificity. The major reactions FMOs catalyze are nucleophilic hetero-atom compounds such as nitrogen, sulfur or phosphorus as the hetero-atom to form N-oxides, S-oxides or P-oxides respectively. Despite the functional overlap with cytochrome P450s, the mechanism of action differs. FMOs bind and activate molecular oxygen before the substrate binds to the enzyme (picture). They also require flavin adenosine dinucleotide (FAD) as a cofactor. Unlike cytochrome P450 enzymes, FMOs are heat-labile, a useful way to distinguish which enzyme system is at work for researchers studying metabolism. Also, FMOs are not inducible by substrates, unlike the P450 enzymes.\n(1) NADPH binds to the enzyme and reduces the prosthetic group FAD to FADH2. NADP+ remains bound to the enzyme.\n(2) Incorporation of molecular oxygen to form a hydroperoxide.\n(3) A peroxide oxygen is transferred to the substrate.\n(4) Water is released.\n(5) NADP+ dissociates returning the enzyme to its initial state.\n\nTo date, there are 6 isozymes of FMO (FMO1-6) in humans, the most prominent and active one being FMO3. The FMO6 gene does not encode for a functional enzyme although it has the greatest sequence similarity with FMO3 (71%), whilst the others range from 50-58% sequence similarity with FMO3. FMO1-3 are the ones that exhibit activity towards nucleophiles, the others are insignificant in this respect (Cashman 2003, Krueger & Williams 2005).
所含基因
3 个基因