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华南师范大学:《医学分子生物学》第七章 信号转导(signal transduction)(董彩虹)

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Cell Signaling General Principles of Cell Signaling 三、 Signaling mediated by Intracellular Receptors Signaling Mediated by Cell-Surface Receptors

Cell Signaling 一、General Principles of Cell Signaling 二、Signaling Mediated by Intracellular Receptors 三、Signaling Mediated by Cell-Surface Receptors

Grey boxes: general components of signaling pathways factor bindir domain White boxes: specific examples Receptor gan Cell kinas membrane Receptors Enzymatic intracellular Altered domain metabolism Protein kinase activity Intracellular mediators messengers (cytoplasmic molecul Adaptor protei Docking proteins Nuclear events Effector GTP-binding proteins enzymes Other Protein or lipid kinases phosphodiesterases Metabolic enzymes Transcription factors Nucleus Nature 411: 759(2001) Changes in Nuclear membrane gene expression

Grey boxes: general components of signaling pathways White boxes: specific examples Ligand  Receptors  Intracellular mediators  Nuclear events Nature 411: 759 (2001)

Cell Signaling General Principles of Cell Signaling 三、 Signaling mediated by Intracellular Receptors Signaling Mediated by Cell-Surface Receptors 1.lon-Channel-Linked Receptors

Cell Signaling 一、General Principles of Cell Signaling 二、Signaling Mediated by Intracellular Receptors 三、Signaling Mediated by Cell-Surface Receptors 1. Ion-Channel-Linked Receptors

OO coo Subunit folds into four MI M2 M1 M2 M8 M4 Acetylcholine binding sites y Outside M1 M4 M2 M3 (B, 1, 8 are homologous Inside M2 amphipathic helices

acetylcholine bindin site lipid channel bilayer ore 4 nm CYTOSOL gate A Model for the structure of the nicotinic(烟碱型) Acetylcholine Receptor Five homologous subunits combine to form a transmembrane aqueous pore. n its closed conformation, the pore is thought to be occluded by the hydrophobic side chain of five leucine residues which form a gate near the middle of the lipid bilayer

A Model for the Structure of the Nicotinic(烟碱型) Acetylcholine Receptor Five homologous subunits combine to form a transmembrane aqueous pore. In its closed conformation, the pore is thought to be occluded by the hydrophobic side chain of five leucine residues which form a gate near the middle of the lipid bilayer

2 Acetylcholine Clo Open YEllow: Leu residues Blue: polar residues

Yellow: Leu residues Blue: polar residues

Cell Signaling General Principles of Cell Signaling 三、 Signaling mediated by Intracellular Receptors Signaling Mediated by Cell-Surface Receptors 1. lon-Channel-Linked Receptors 2. G-Protein-Linked Receptors or G-Protein-Coupled Receptors (GPCR)

Cell Signaling 一、General Principles of Cell Signaling 二、Signaling Mediated by Intracellular Receptors 三、Signaling Mediated by Cell-Surface Receptors 1. Ion-Channel-Linked Receptors 2. G-Protein-Linked Receptors or G-Protein-Coupled Receptors (GPCR)

G蛋白偶联型受体及其信号转导 G蛋白偶联型受体:七次跨膜受体 信号传递的基本过程: 激活 配体+受体一>G蛋白效应分子→小分子信使靶分子→一产生效应 或抑制 (第二信使)

G蛋白偶联型受体及其信号转导 • G蛋白偶联型受体:七次跨膜受体 • 信号传递的基本过程: 配体+受体 G蛋白 效应分子 小分子信使 (第二信使) 靶分子 产生效应 激 活 或抑制 激 活

G蛋白偶联区

G蛋白的种类:激动型G蛋白(Gs)、抑 制型G蛋白(Gi)、磷脂酶C型G蛋白(Gp) G蛋白的类型a亚基 功能 Gs a、激活腺苷酸环化酶 a1|抑制腺苷酸环化酶 激活磷脂酰肌醇特异的磷脂酶C Go an|大脑中主要的G蛋白、可能调节离子通道

• G蛋白的种类 : 激动型G蛋白(Gs)、抑 制型G蛋白(Gi) 、磷脂酶C型G蛋白(Gp) G蛋白的类型 α亚基 功能 Gs Gi Gp Go αs αi ? αo 激活腺苷酸环化酶 抑制腺苷酸环化酶 激活磷脂酰肌醇特异的磷脂酶C 大脑中主要的G蛋白、可能调节离子通道

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