Signal-4-临床五年制课件.ppt

;Questions: Please briefly describe the process of the following signaling pathways (1) cGMP dependent PKG pathway ;(2) Ca2+-DAG-dependent PKC pathway; (3)Ca2+-CaM dependent PK pathway;(4)Ras-MAPK pathway; (5) JAKs-STAT pathway; (6) TGF-β pathway; (7) NF-κB pathway ; ;1. Signal transduction pathways mediated by membrane receptors 2. Signal transduction pathways mediated by intracellular receptors; Intracellular receptor (transcription regulated receptor);;NR的分类;NR的分类;NR的分类;NR的分类;2. Signal transduction pathways mediated by intracellular receptors 2.1 Signal transduction pathway mediated by cytosolic receptor 2.2 Signal transduction pathway mediated by intranuclear receptor ;Intracellular receptor-mediated pathways;Action of intracellular receptor ;核受体介导转录调控的基本过程;;Mediator is a multiprotein complex that functions as a transcriptional coactivator in all eukaryotes. It was discovered by Roger D. Kornberg, winner of the 2006 Nobel Prize in Chemistry. It is also referred to in scientific literature as the vitamin D receptor interacting protein (DRIP) coactivator complex and the Thyroid Hormone Receptor-associated Proteins (TRAP).;CTD: YSPTSPS;中介体复合物在基因转录调控中的作用和机制;中介体复合物直接与Pol II和通用转录因子发生相互作用 中介体复合物对转录的双向调控 两种形式:中介体复合物和CDK8-中介体复合物 中介体复合物:激发依赖于激活因子的转录 CDK8-中介体复合物CDK8可以通过磷酸化TFIIH的cyclin H亚基, 使TFIIH无法磷酸化Pol II CTD, 进而抑制转录 ;PIC在启动子上的装配;TFⅡH导致的CTD磷酸化可促使RNA聚合酶Ⅱ起始转录;Ligands for Intracellular receptors ● Steroid Hormone ◆ Cytosolic R: Glucocorticoid （糖皮质激素） ◆ Intranuclear R: estrogen（雌激素）, androgen（雄激素）, progesterone （孕酮） ● VD3: Intranuclear R ● Thyroxin: Intranuclear R ;2.1 Signal transduction pathway mediated by cytosolic receptor Glucocorticoid （such as cortisol,考的松) Cytosolic R nucleus cis-acting element gene expression; Why gluco