信号转导系统
植物免疫系统中的信号转导通路
植物免疫系统中的信号转导通路植物无法逃离环境的威胁，它们只能通过不同的机制来对抗病原体和有害环境。
植物的免疫系统包括两个主要方面：基础免疫和适应性免疫。
基础免疫是植物对常见的病原体和环境应激的回应，而适应性免疫则是植物对先前未遇到的特定病原体的特异反应。
植物在免疫应答中涉及到一系列的信号转导通路，最终导致基因表达的改变和产生免疫反应。
下面，我将详细介绍植物免疫系统中的信号转导通路。
1. PAMPs信号通路PAMPs (Pathogen-Associated Molecular Patterns) 信号通路是植物基础免疫的一个重要部分。
PAMPs 是微生物体表面上的分子，如蛋白质、多糖和核酸。
它们是微生物的“指纹”，可以被植物的受体感知。
当一个 PAMPs 被植物受体识别后，植物会产生一系列的信号转导反应，导致基因表达的改变和免疫应答的触发。
这些反应包括钙离子（Ca2+）信号、PIP2 次级信号、激活蛋白激酶（MAPK）模块、NADPH 氧化酶的激活、转录因子激活等。
此外，PAMPs 信号通路还涉及一些基因的转录，例如 WRKY、MYB、NAC和 ERF 家族转录因子等。
这些转录因子能够导致基因的表达变化，从而激发免疫应答。
2. R蛋白信号通路R 蛋白（Resistance proteins）信号通路是植物适应性免疫的关键组成部分。
R蛋白能够识别细菌、真菌和病毒等寄生性微生物。
当一个 R 蛋白识别到目标病原体时，它会形成一个信号复合物，促进一系列的信号转导反应。
这些反应包括活化特异性NADPH 氧化酶、活化植物激酶（PIK）、活化 MAPK 和其他激酶以及调控转录因子的激活等。
R 蛋白信号通路还包括一些特定的转录因子，例如：TGA 转录因子和 EDS1 转录因子。
TGA 转录因子是一种可激活植物抗氧化酶的DNA结合蛋白。
EDS1 转录因子在植物免疫应答中起着重要的作用，它与 PAD4、NPR1 等蛋白质相互作用，调节免疫反应基因的表达。
电信号转导在神经系统中的作用机制
电信号转导在神经系统中的作用机制神经系统是人体中一个复杂而精密的系统，它通过电信号的传导来实现各种生理功能和情绪反应。
电信号转导机制是神经系统正常运行所必需的重要过程。
本文将讨论电信号转导在神经系统中的作用机制，从神经元活动到信息传递的各个环节进行深入探究。
首先，电信号转导起始于神经元的电活动。
神经元是神经系统的基本功能单位，它具有细胞体、树突、轴突等多个组分。
在神经元细胞体内，存在着许多离子通道，如钠离子通道和钾离子通道。
这些离子通道负责离子的进出，进而形成起始动作电位。
当神经元受到刺激时，离子通道会发生打开或关闭的变化，导致细胞内外电势差的改变。
如果这个改变足够大，就会发生电势的反转，进而产生动作电位。
动作电位的产生是神经信号传导的基础。
其次，电信号的传导依赖于神经元的轴突。
轴突是神经元的一个长且细长的延伸，负责将电信号从细胞体传递到其它神经元或效应器（例如肌肉和腺体）。
轴突表面存在着髓磷脂鞘，它是由一层层髓鞘细胞膜紧密包裹形成的。
髓鞘充当着电信号传导的绝缘体，类似于电线的绝缘层，减少信号的损失和交叉干扰。
而髓鞘间隙，则是一段一段没有髓鞘保护的轴突部分，叫做"节点"。
节点处存在大量的钠离子通道，这使得在信号传导过程中电信号得以快速跳过节点，以提高传导速度。
这种特殊的结构被称为盐atoryconduction（"盐"是法语"salt"的意思，意味着快速）。
此外，电信号转导涉及到神经元之间的化学传递。
当动作电位到达神经元的轴突末梢时，它会刺激释放化学物质，称为神经递质。
神经递质是通过神经元与神经元之间的突触传递的，跨过突触间隙，作用于下一个神经元。
突触间隙是两个神经元之间的微小间隙，通常只有20-30纳米宽度。
神经递质通过被释放到突触间隙中，并与接受体结合来传递信号。
接受体是位于突触后膜上的蛋白质，能够识别和结合特定的神经递质分子。
当神经递质与接受体结合时，可以引发离子通道的开放或关闭，进而改变细胞的电位。
信号转导系统
信号转导系统信号转导生物体对环境(包括外环境和内环境)信号变化有极高的反应性。
如细菌趋向营养物的运动，视觉细胞对光的感觉，饥饿时激素信号使燃料分子(feul molecules)如糖、脂肪、蛋白质等释放内部能量，生长因子诱导分化等都是典型的例子。
细胞对外界刺激的感受和反应都是通过信号转导系统(signal transduction system)的介导实现的。
该系统由受体、酶、通道和调节蛋白等构成。
通过信号转导系统、细胞能感受、放大和整合各种外界信号。
第一节细胞信号的概况一、细胞外信号分子的识别在多细胞高等生物体内，细胞间的相互影响是通过信号分子实现的，信号分子包括蛋白质、肽、氨基酸、核苷酸、类固醇、脂肪酸衍生物和一些溶于水的气体分子，如一氧化碳、一氧化氮等。
这些信号分子大多数由信号细胞(signaling cells)分泌产生，有些是通过扩散透过细胞膜释放，有些则是和细胞膜紧密结合，需要通过细胞接触才能影响到和信号细胞相接触的其他细胞。
信号分子对靶细胞的作用都是通过一类特异的蛋白质——受体实现的，受体能特异地识别信号分子。
靶细胞上的受体大多数是跨膜蛋白质(transmembrane proteins)，当受体蛋白和细胞外信号分子(也称配体ligand)结合后就被激活，从而启动靶细胞内信号转导系统的级联反应(cascade)。
有些受体位于细胞内，信号分子必须进入细胞才能与受体结合，并使受体激活，这些信号分子都是分子量很小而且是脂溶性的，能扩散通过细胞膜进入细胞。
二、分泌性信号分子作用途径旁分泌(paracrine)由细胞分泌的信号分子只是作为局部的介导物，作用于邻近的靶细胞，称为旁分泌。
旁分泌的信号分子由细胞分泌后，不能扩散至较远的距离，这种信号分子很快地被邻近的靶细胞摄入，或被细胞外酶降解(图17-1A)。
突触(synapses)在较高等的多细胞生物体内，神经细胞(或神经元)能通过轴突与相距较远的靶细胞接触。
细胞生物学第11章-细胞通讯与信号转导
（3）不同的细胞通过各自的受体，对胞外信号应答， 产生相同的效应。如：肝细胞肾上腺素受体和胰 高血糖素受体结合各自的配体激活以后，都能促 进血糖的升高。
（4）一种细胞具有一套多种类型的受体，应答多种 不同的胞外信号，从而启动细胞的不同生物学效 应。
（３）自分泌（autocrine）：
细胞对自身分泌物产生反应，常见于病理 条件下。如：肿瘤细胞合成释放生长因子刺 激自身。
（4）化学突触传递神经信号：
神经细胞兴奋后，动作电位的传递，引起突 触前突起终末分泌化学信号，扩散至突触后细 胞，实现电信号和化学信号之间的转换。
2 通过细胞的直接接触（contactdependent signaling）：即细胞间接 触性依赖的通讯
（3）气体信号分子： 第一个发现的气体信号分子是NO，可以进入细胞直 接激活效应酶，参与体内众多的生理和病理过程。
2. 受体（receptor）
是一种能够识别和选择性结合某种配体的大分子, 通过和配体的结合，经信号转导作用，最终表现为生 物学效应。
▪ 受体的结构特点：
多为糖蛋白，至少包含配体结合区和效应区2个 功能区域，分别具有结合特异性和效应特异性。
▪ 特异性 ▪ 放大作用 ▪ 信号终止或下调特征 ▪ 整合作用
第二节
细胞内受体介导的信号传递
一、细胞内受体与基因表达
细胞内受体活化的机制：
激活前：受体和抑制性蛋白结合成复合物 激活后：如果甾类激素和受体结合，导致抑制
性蛋白从复合物上解离下来，使受体暴露出 DNA结合位点，激素－受体复合物与基因调 控区（激素应答元件，hormone response element, HRE）结合，影响基因的转录。
细胞生物学总结(复习重点)——8.细胞信号转导
4、细胞通讯：一个细胞发出的信息通过介质传递到另一个细胞产生相应的反应。
对于多细胞生物体的发生和组织的构建，协调细胞的功能，控制细胞的生长、分裂、分化和凋亡是必须的。
包括分泌化学信号（内、旁、自、化学突触）、细胞间接触、和相邻细胞间间隙连接。
5、细胞识别：细胞通过其表面的受体与胞外信号物质分子（配体）选择性地相互作用，进而导致胞内一系列生理生化变化，最终表现为细胞整体的生物学效应的过程。
20、信号分子：生物体内的某些化学分子，如激素、神经递质、生长因子、气体分子等，在细胞间和细胞内传递信息，特称为信号分子。
21、信号通路：细胞接受外界信号，通过一整套的特定机制，将胞外信号转导为胞内信号，最终调节特定基因的表达，引起细胞的应答反应，这种反应系列称为细胞信号通路。
22、受体：一种能够识别和选择性地结合某种配体（信号分子）的大分子，当与配体结合后，通过信号转导作用将胞外信号转导为胞内化学或物理的信号，以启动一系列过程，最终表现偶联型受体和酶偶联的受体。
23、第一信使：一般将胞外信号分子称为第一信使。
24、第二信使：细胞表面受体接受胞外信号后最早在胞内产生的信号分子。
细胞内重要的第二信使有：cAMP、cGMP、DAG、IP3等。
第二信使在细胞信号转导中起重要作用，能够激活级联系统中酶的活性以及非酶蛋白的活性，也控制着细胞的增殖、分化和生存，并参与基因转录的调节。
10、IP3IP2IP4。
DG通过两种途径终止其信使作用：一是被水解成单脂酰甘油。
13、分子开关：在细胞内一系列信号传递的级联反应中，必须有正、负两种相辅相成的反馈机制精确调控，也即对每一步反应既要求有激活机制，又必然要求有相应的失活机制，使细胞内一系列信号传递的级联反应能在正、负反馈两个方面得到精确控制的蛋白质分子称为分子开关。
25、G—蛋白：由GTP控制活性的蛋白，当与GTP结合时具有活性，当与GDP结合时没有活性。
既有单体形式（ras蛋白），也有三聚体形式（Gs活Gi抑）。
信号转导系统（Signaltransductionsystem）
信号转导系统（Signal transduction system）signal transductionOrganisms are highly responsive to changes in the environment (including external and internal environments). If the bacteria tend to nutrient movement, feeling the visual cells to light, hunger hormone signal (feul molecules) of the fuel molecules such as sugar, fat, protein and other internal energy release, growth factor induced differentiation are typical examples. The sensation and response of cells to external stimuli are mediated by signal transduction (system). The system consists of receptors, enzymes, channels, and regulatory proteins. Through the signal transduction system, cells can sense, amplify and integrate various external signals.Section 1 general situation of cellular signalRecognition of extracellular signaling moleculesIn higher multicellular organisms, interaction between cells is achieved by signal molecules, signaling molecules including proteins, peptides, amino acids, nucleotides, steroids, fatty acid derivatives and some water soluble gases, such as carbon monoxide and nitric oxide. Most of these signal molecules by signal (signaling cells) secreted by cells, some by diffusion through the cell membrane and release, some are the cell membrane closely, other cells by cell contact can affect cell contact and signal.Signaling molecules act on target cells through a specificclass of proteins, receptors, which recognize the signaling molecules in particular. Most of the target cell receptor is a transmembrane protein (transmembrane proteins), when the receptor protein and extracellular signal molecules (also known as ligand binding ligand) was activated, thus starting the cascade target intracellular signal transduction system (cascade). Some receptors located in intracellular signaling molecules must enter the cell binding to receptors and receptor activation, these signal molecules are very small and the molecular weight is fat soluble and can diffuse into the cell through the cell membrane.Two, secretory signaling molecules, action pathwayParacrine (paracrine)Signaling molecules secreted by cells act only as local receptors, acting on adjacent target cells, called paracrine. Paracrine signaling molecules secreted by the cells, can not spread to the far distance, the target cell signaling molecules quickly near the intake, or by extracellular enzyme degradation (Figure 17-1A).Synapse (synapses)In higher multicellular organisms, nerve cells (or neurons) can communicate with distant target cells through axons. When the nerve cells in the environment or to receive signals from other cells are activated, can transmit electrical impulses along the axon, pulse arrival axon terminal nerve endings, can stimulate peripheral secretion of neurotransmitter (neurotransmitter).Nerve terminals contact the chemical synapse and postsynaptic target cells and release neurotransmitters to target cells (Fig. 17-11B).endocrineThe hormone secreting signaling cells are called endocrine cells, and hormones produced by endocrine cells enter the bloodstream and then reach the target cells in other parts of the organism (Fig. 17-1C). The endocrine signal is slower than the synaptic signal, because the former is slowed by blood, and the latter is not only fast but accurate.Autocrine (autocrine)There is a signaling pathway associated with the same cell, or the target cell of the signal is the cell that produces the signal itself, which is called autocrine. In vivo development and differentiation process, once a cell has directed differentiation, the cells can secrete autocrine signaling molecules to enhance the differentiation process of this specific, therefore autocrine signaling is thought to be an organism in early developmental stage with "community effect" (community effect) based mechanism.Gap junction (gap, junction)A signaling molecule that enables neighboring cells to collaborate via gap junctions. This channel, which connects the cell membrane directly, allows cells to exchange small molecules of intracellular signaling molecules such as Ca2+ andcAMP, but macromolecules signaling molecules cannot pass.Second types of cell membrane receptorsThe receptor is a kind of special protein located on the cell membrane or intracellular signaling molecules, can specifically recognize and bind with them, thus starting the cascade of intracellular signal transduction system. Depending on where cells are located, receptors can be divided into cell membrane receptors and intracellular receptors. Cell membrane receptor proteins account for only a small proportion of total protein, only 0.01%, and therefore are difficult to purify. Because of the development of recombinant DNA technology, cloning of receptor protein genes can greatly promote the study of receptor proteins. There are three types of cell membrane receptor proteins: ion channel coupled receptors (ion-channel, coupled, receptors), G protein coupled receptors (G-protein, coupled, receptors), and receptors (enzyme coupled). As a signal transduction conductor, membrane receptors can bind to extracellular signaling molecules with high affinity and convert extracellular signals into one or more signals within the cell, thereby altering cellular biological behavior.Ion channel coupled receptorIon channel coupled receptors are involved in the rapid transmission of synaptic signals between electrically excitable cells, which are mediated by a subset of neurotransmitters. Binding of neurotransmitters to the receptor alters the structure of the receptor, allowing ions to enter the postsynaptic cells through the channels that aremade up of receptor proteins, and alter the excitability of postsynaptic cells, as shown in figure 17-2.Two, G protein coupled receptorThe G protein coupled receptor indirectly regulates other membrane-bound targets that may be enzymes or ion channels. The connection between receptor and target protein is achieved by GTP binding regulatory protein (G protein). If the target protein is the target protein enzyme, so the activation can change the concentration of molecules related to signal transduction in cells; if the target protein is ion channels, you can change the cell membrane permeability of ions, as shown in figure 17-3.Three 、 enzyme coupled receptorIn combination with signaling molecules, the receptor protein itself acts as an enzyme, or activates other enzymes associated with the receptor. The ligand binding sites of such receptors are located outside the cell and the catalytic site is within the cell, as shown in figure 17-4. The enzyme activity of these receptors is mainly protein kinase activity, or protein kinase related activity, which catalyzes the phosphorylation of protein related to signal transduction in target cells.The third section is a signal transduction system mediated by G protein coupled receptorsG protein coupled receptor familyG protein coupled receptors are one of the largest family of cell membrane receptors. More than one hundred species of these receptors have been found in mammals. This family receptor can bind to many signaling molecules, including hormones, neurotransmitters, and local mediators. From a chemical structure, signal molecules can be proteins, peptides, amino acids and derivatives of fatty acids. The same signaling molecules can bind and activate different members of this receptor family; for example, epinephrine can bind to and activate at least 9 G protein coupled receptors. Structurally, the members of this receptor family are very similar. They are all transmembrane proteins with only one polypeptide chain. The transmembrane portion is composed of 7 discontinuous peptide segments, as shown in figure 17-5. This receptor family is, in terms of biological evolution, conserved not only in the structure of proteins but also functionally. Because whether in unicellular organisms or in multicellular organisms, they are able to receive extracellular signals and then transduce them to G proteins.Two, trimeric GTP- binding protein (trimeric, GTP-binding, proteins, G protein)G is a class of membrane proteins that bind to GTP or GDP and have GTP enzyme activity on the cytoplasmic surface of the cell membrane, and their activity depends on whether they bind GTP or GDP. When combined with GTP, the G protein is active and is not active when combined with GDP. The active G protein stimulates other components of the intracellular signaling system. G proteins can be divided into two groups, one is the trimeric GTP- binding protein as an extracellular signaltransducer, and the other is a monomeric GTP- binding protein (also known as the monomeric GTP enzyme) that acts on intracellular signaling. Generally referred to as the G protein, the trimeric GTP- binding protein is composed of three different subunits, namely, alpha subunit, beta subunit, and gamma subunit.The G protein has many kinds, are common to activate adenylate cyclase stimulatory G protein (stimulatory G, protein, Gs), inhibition of adenylate cyclase inhibitory G protein (inhibitory G, protein, Gi) and phospholipase C- (activation of phospholipase C- beta beta, a specific role of phospholipase C in lipositol Gq). G protein also has the activity of GTP enzyme, and the GTP bound to G protein is GDP, thus inactivating the G protein.Three and second messengers (second, messengers)Most of the G protein coupled receptor can activate the chain reaction, changing the concentration of one or several kinds of small signalling molecules within the cell, through these small signal molecules will further signals, such as cAMP, Ca2+, IP3 and DG etc., usually this kind of signal transduction in cells of small molecular compounds called second messenger. CAMP and Ca2+ are two kinds of a more comprehensive understanding of the intracellular messenger, in most animal cells, two different reaction pathways to stimulate the two intracellular messenger concentration changes, most of the G protein coupled receptor is only the regulation of a signal transduction pathway, as shown in figure 17-6.Four, through the cAMP signal transduction system(1) the receptor controls cAMP concentration by modulating adenylate cyclaseAs an intracellular messenger, the concentration of cAMP varies considerably, and in cellular responses to hormones, the concentration of cAMP varies more than 5 times in seconds.The mechanism of this rapid reaction is achieved by two enzymes, adenylyl cyclase and cAMP phosphodiesterase. The substrate of adenylate cyclase is ATP, and the product is cAMP, which is a cell membrane binding protein. Phosphodiesterase can rapidly hydrolyze cAMP to produce 5 '-AMP, as shown in figure 17-7. Extracellular signals control cAMP levels mainly by altering adenylate cyclase activity rather than phosphodiesterase activity. Combination of different hormones and receptors on the membrane of target cells, some by the Gs protein activates adenylate cyclase and increased the intracellular cAMP concentration, such as thyroid stimulating hormone, adrenocorticotropic hormone, luteinizing hormone, parathyroid hormone, epinephrine, glucagon, antidiuretic hormone; some by Gi protein inhibits adenylate cyclase, can reduce the intracellular concentration of cAMP. Alpha 2 - adrenergic receptor coupled with Gi protein, beta adrenergic receptor coupled with Gs protein, so the combination of epinephrine and receptor through with different types of G protein, stimulate or inhibit adenylate cyclase, thereby controlling the intracellular concentration of cAMP.(two) the mechanism of activation of G protein coupledreceptors to adenylyl cyclaseIn the signal transduction mediated by G protein, a G protein by GTP hydrolysis activity of GTP to GDP, re formed activated heterotrimeric G protein, the G protein signal transfer is conducive to the timely termination of receiving a signal protein G. On the other hand, when the signal molecules exist for a long time, a specific G protein coupled receptor kinase (G-protein coupled receptor kinases, GRK) the G protein coupled receptor C-terminal multiple serine residues phosphorylated, which coupled receptors and G protein; also capture protein (arrestin) can recognize and bind phosphorylation of the receptor, blocking the interaction between receptor and G protein.(three) cAMP dependent protein kinase mediates the cAMP effectIn animal cells, cAMP exerts its biological effects mainly by activating cAMP dependent protein kinases (protein, kinase, A, PKA, A). PKA catalyzes the transfer of the terminal phosphate groups of ATP molecules to specific serine residues or threonine residues on selected target proteins, which are covalently phosphorylated amino acid residues, thereby modulating the activity of the target protein. The inactive state of PKA has two identical catalytic subunits and two identical regulatory subunits that regulate subunit binding to cAMP. When the cAMP and regulatory subunit combination, conformation of the subunit changes the regulatory subunit from the enzyme molecule disassociated, catalytic subunit from catalytic activation, substrate protein phosphorylation, as shown in figure 17-9. Epinephrine and skeletal muscle cellmembrane beta adrenergic receptor, Gs protein by intracellular adenylate cyclase activation, elevated cAMP, cAMP activated PKA, PKA two kinds of enzyme phosphorylation, a phosphorylase kinase, the enzyme was phosphorylated and activated and the activation of glycogen phosphorylase, finally the glycogen decomposition (Fig. 17-10). Another enzyme that is phosphorylated by PKA is glycogen synthase, which is inactivated by phosphorylation. Thus, the blood glucose levels are elevated by the action of these two enzymes, which promote glycogen breakdown and inhibit glycogen synthesis.In some animal cells, the increase in cAMP concentration activates transcription of some specific genes. For example, in a cell that secretes a growth hormone releasing hormone (somatostatin or GHRIH) (the hypothalamus and pancreas delta cells), cAMP can open up genes encoding the hormone. The regulatory region of such genes has a short sequence of cis elements called cAMP response elements (cAMP, response, element, CRE) that recognize CRE transcription factors known as CRE binding proteins, referred to as CREB. When CREB is phosphorylated by PKA and combined with CRE, it promotes transcription of the genes involved.The biological effects of cAMP are transient because there is a mechanism in the cell that allows the phosphorylation of PKA phosphorylated proteins to catalyze the dephosphorylation of serine / threonine phosphoprotein phosphatases.Five, through the Ca2+ signal transduction systemCa2+ acts as a cellular signal in many cellular responses, suchas cell proliferation, secretion, muscle contraction, and rearrangement of the cytoskeleton. The intracellular Ca2+ concentration was very low, less than 10-7M, much lower than the Ca2+ concentration in the extracellular fluid. The endoplasmic reticulum, mitochondria and sarcoplasmic reticulum of cells are repositories of intracellular Ca2+. Many signaling molecules cause extracellular fluid Ca2+ influx or subcellular release of Ca2+, resulting in rapid increases in cytosolic Ca2+, regulating various activities of life. Ca2+ signal in two ways: in the presence of nerve cells in a way, when the cell membrane depolarization (depolarization) caused Ca2+ into nerve endings, start neurotransmitter secretion, the content will be described in detail in physiology; another way is to combine the extracellular signal and G protein coupled receptor and signal transduction to the endoplasmic reticulum, the endoplasmic reticulum in the cytoplasm by Ca2+ released into the cytoplasm, Ca2+ cell response control.(1) activation of phosphoinositide signaling pathways via G protein coupled receptorsPhospholipid (inositol) is located in the inner layer of the phospholipid bilayer of the cell membrane. The inositol phospholipid associated with signal transduction is the phosphorylated derivative of phosphatidylinositol (phosphatidylinositol, PI): PI monophosphate (PIP) and PI two phosphate (PIP2). The relationship between PI, PIP2, and inositol three phosphate (inositol, trisphosphate, IP3) is shown in figure 17-11. After binding and activation of the receptor by extracellular signaling molecules, the G protein is activated, and the Gq protein activates phospholipase C-beta, which is attached to the cell membrane, and then phospholipase C- beta causes PIP2 cleavage. Two molecules are produced: IP3 and two DG (diacylglycerol), both of which play an important role in signal transduction (Fig. 17-12). The role of phosphoinositide signaling pathway of extracellular signal such as hormone, vasopressin (vasopressin); there are neurotransmitters such as acetylcholine (acting on pancreatic and smooth muscle); antigen (in mast cells); a thrombin (acting on platelet) etc..(two) the role of IP3 and DGPIP2 IP3 is produced by the hydrolysis of small molecules of water soluble, leaving the membrane can quickly spread in the cytoplasm, specific Ca2+- channel IP3 and endoplasmic reticulum binding, can make the endoplasmic reticulum cavity Ca2+ release into the cytosol, and the release of Ca2+ has a positive feedback effect, which is released Ca2+ binding to the Ca2+ channel, and then promote the release of Ca2+.The important role of DG is to activate protein kinase C (protein, kinase, C, PKC), and PKC is a class of Ca2+ dependent protein kinases that enable selective phosphorylation of serine / threonine residues of target proteins. Because of the action of IP3, Ca2+ in cytoplasm can transfer PKC from cytoplasm to cytoplasmic surface of cell membrane. Activation of PKC in Ca2+, DG, and phosphatidylserine in cell membrane phospholipid components. The highest concentration of PKC in mammalian midbrain cells is the phosphorylation of ion channel proteins in neurons, thereby altering the excitability of nerve cell membranes. In many cells, PKC can regulate the expression ofrelated genes by activating phosphorylation cascades and finally phosphorylation and activation of some transcription factors.(three) the action of CalmodulinCalmodulin (calmodulin) is a specific Ca2+ binding protein that exists in almost all eukaryotic cells. As intracellular Ca2+ receptors, calmodulin mediates a variety of biological processes regulated by Ca2+. The primary structure of calmodulin is highly conserved, with only one polypeptide chain, containing about 150 amino acid residues, and having 4 high affinity calcium binding sites. The conformation changes after binding with Ca2+. Ca2+ activates calmodulin by allosteric action. The Ca2+- calmodulin complex is capable of binding to a variety of target proteins and altering the activity of target proteins. These target proteins have a variety of enzymes and transporters on the cell membrane, such as the Ca2+-ATP enzyme on the cell membrane (which pumps Ca2+ out of the cytoplasm). However, the effect of Ca2+- calmodulin is mediated mainly by the Ca2+- calmodulin dependent protein kinase (CaM kinase). CaM kinase also activates target proteins by phosphorylation of specific serine or threonine on target proteins. CaM kinase has a wide range of specificity, suggesting that these enzymes mediate multiple roles in Ca2+ in animal cells.Six, the interaction of cAMP and Ca2+ pathwaysAlthough cAMP intracellular signaling pathways and Ca2+ intracellular signaling pathways are two independent pathways, they also interact with each other. First, intracellular Ca2+levels and cAMP levels interact with each other, such as adenylyl cyclase and phosphodiesterase, which are directly related to the level of cAMP, are regulated by the Ca2+- calmodulin complex. PKA is capable of phosphorylation of some Ca2+ channels and Ca2+ pumps, enabling them to alter activity, such as PKA phosphorylation of IP3 receptors on the endoplasmic reticulum, and initiation or inhibition of IP3 induced release of Ca2+. Second, enzymes that are regulated directly by Ca2+ and cAMP interact with each other, as some CaM kinases can be altered by phosphorylation of PKA. Third, these enzymes can interact with a number of target molecules, in which PKA and CaM kinases are phosphorylated in different parts of some proteins.Fourth enzyme coupled receptor mediated signal transduction systemEnzyme coupled receptors and G protein coupled receptor is a kind of membrane protein, and the domain of extracellular signal molecules in the cell membrane, cytoplasmic domain within the cell itself has enzyme activity, or directly associated with other enzymes. There are 5 types of enzyme coupled receptors known as receptor kinases cyclase (receptor, guanylyl, cyclases), and receptor tyrosine kinase (receptor, tyrosine, and tyrosine);③酪氨酸激酶相关受体 (tyrosine - kinase associated receptors);④受体酪氨酸磷酸酶(receptor tyrosine phosphatases); ⑤受体丝氨酸／苏氨酸激酶 (receptor serine／threonine kinases).本章只介绍前三种酶偶联受体介导的信号转导系统.一、受体鸟苷酸环化酶信号转导系统这类受体与细胞外信号分子结合后, 能催化细胞质内cgmp的生成,因该跨膜受体的胞质结构域具有鸟苷酸环化酶活性, 催化gtp生成cgmp, cgmp再激活cgmp依赖的蛋白激酶 (cgmp dependent protein kinase, g激酶), g激酶能使靶蛋白上的丝氨酸或苏氨酸残基磷酸化, 激活靶蛋白.在此信号转导系统中, cgmp是细胞内信号分子.与camp信号不同之处是: 在camp信号途径中联系受体与环化酶的是g蛋白, 而在cgmp信号途径中此联系通过受体本身.但在某些细胞中, 如视觉细胞, cgmp的生成也通过g蛋白.通过受体鸟苷酸环化酶途径的细胞外信号, 有心钠素等.二、受体酪氨酸激酶信号转导系统(一) 受体酪氨酸激酶第一个被确认具有酪氨酸特异的蛋白激酶活性的受体是表皮生长因子 (epidermal growth factor, egf) 受体.egf受体只有一条肽链, 约有1200个氨基酸残基.当egf与egf受体结合后, 受体的细胞质酪氨酸激酶结构域即被激活, 激活的酪氨酸激酶能选择性地使受体蛋白本身的酪氨酸残基或其他靶蛋白上的酪氨酸残基磷酸化.现已发现, 大多数生长因子和分化因子的受体都属这一类受体, 这些受体都可以通过自身磷酸化 (car phosphorylation) 来启动细胞内信号的级联反应.(二) 受体酪氨酸激酶信号转导系统中的其他成分1.具有sh结构域的蛋白质这类蛋白质不是指含有sh基团 (巯基) 的蛋白质, 而是指最初在src (一种癌基因) 蛋白中发现的一段序列, sh是src同源性 (src homology) 的缩写.已发现有许多种含有sh结构域的蛋白质, 如gtp酶激活蛋白 (gtpase - activating protein,gap), 磷脂酶c -. gamma. (plc - γ作用与plc - β相同), 类src非受体型蛋白酪氨酸激酶src - like nonreceptor protein tyrosine kinase), irs 1等.这些蛋白质都具有两种sh结构域 - - sh2和sh3.sh2能识别磷酸化的酪氨酸残基, 使含有sh2的蛋白质与激活的受体酪氨酸激酶结合.sh3的作用是与细胞内其他蛋白质结合.在具有sh2和sh3的蛋白质中有些是酶蛋白, 如上述gap, plc - γ等, 有的只是作为一种 "连接器", 如生长因子受体结合蛋白(growth factor receptor bound protein2, grb2), 它的作用就是作为连接受体酪氨酸激酶和其他蛋白质的桥梁.2.SOS protein (SOS) SOS can combine with the SH3 domain of GRB2, SOS is a guanine nucleotide exchange factor (guanine, nucleotide-exchange, factor, GEF) can combine with Ras protein, and the original Ras combined with the GDP exchange GTP. When the receptor tyrosine kinase is activated, it acts via GRB2; the translocation of SOS from the cytoplasm to the cytoplasmic surface of the cell membrane approaches the membrane-bound Ras.3.Ras protein (referred to as Ras) Ras belongs to the monomeric GTP enzyme Ras superfamily (Ras superfamily of monomeric GTPase), is located in the cytoplasm of the cell membrane surface membrane bound protein. The GTP enzyme activates the egg liner (GAP) to inactivate Ras with the hydrolysis of Ras bound to GDP, whereas guanine nucleotide exchange factor (GEF) enables the exchange of GDP with Ras to GTP and activates Ras (Fig. 17-15) GTP. Ras plays a central role in signal transduction mediated by receptor tyrosine kinase, a key component that controls cell growth and differentiation. The mutation of Ras leads to the loss of signal transduction and can lead to malignant transformation of cells. Signal transduction pathways and mechanisms involved in theactivation of Ras signaling through extracellular signals (in EGF) are shown in figure 17-16.Ras signaling mediated by 4.Ras downstream of the signal can bind to the N terminal domain of the Raf protein with serine / threonine kinase activity. Raf binding with Ras can bind and phosphorylation of a protein that has both tyrosine kinase activity and serine kinase activity by C ends - MEK. Phosphorylated MEK can make another serine / threonine kinase protein - MAP kinase (microtubule-associated protein or mitogen-activated protein kinase) - phosphorylated and activated. Activated MAP kinase phosphorylation of a variety of different proteins, including transcription factors, and thus play a regulatory role in gene expression. Figure 17-17 is a simple hint of the receptor tyrosine kinase, the Ras signaling pathway.Three, tyrosine kinase related receptor signaling systemThe JAK-STAT signaling pathway is a typical example of the tyrosine kinase related receptor signaling system. This is a relatively simple signaling system with only three components: receptors, JAK kinases, and STAT.(I) tyrosine kinase related receptorThese receptors include receptors for a variety of cytokines (cytokines), such as interferon receptors and interleukin 2 receptors. Such receptors do not in themselves have intrinsic kinase activity, but when extracellular signaling molecules bind to form a two dimer, the receptor two binds to JAK kinaseand activates the JAK kinase.(two) JAK kinaseJAK kinases are a group of molecules with multiple members, each of which can specifically bind to the corresponding cytokine receptor. The JAK kinase originally known as the Janus kinase (Janus means the Janus Janus of the gateway), because this molecule has two kinase domains. JAK kinase belongs to tyrosine kinase, and the major substrate is STAT.(three) STATSTAT is a class of transcription factors, signal, transducers, and, activation, of, transcription acronym. At least 7 kinds of STAT are known,Each STAT is activated by the corresponding JAK kinase, respectively. Phosphorylation of STAT leads to the formation of STAT two dimers, which can be of the same two polymer or two different polymers (). The basis for the formation of a dimer is the interaction between the SH2 domain of the two STAT and phosphorylated tyrosine residues, respectively, on the two. The STAT two is transferred from the cytoplasm to the nucleus and is bound to the cis acting elements to regulate the expression of target genes.The JAK-STAT signal transduction pathway is shown in Figure 17-18The fifth section is a signal transduction system mediated byintracellular receptorsSmall molecule fat soluble (hydrophobic) extracellular signaling molecules include steroids, thyroid hormones, retinoids, vitamin D, etc.. Although these signal molecules differ in structure, the mechanism of signal transduction is the same. These lipid soluble molecules can diffuse into the cytoplasm or nucleus through the cell membrane, and bind with the protein in the cell, and finally through the receptor activated receptors to regulate gene expression, so this type of cellular receptor is a trans acting factor. These receptors are known as the intracellular receptor superfamily (intracellular, receptor, superfamily) or the steroid receptor superfamily (steroid-hormone, receptor, superfamily).I. the domain of the intracellular receptorThese receptors have two domains, namely, the DNA binding domain, the hormone binding domain, and a region of change (Fig. 17-19). The DNA binding domain of different receptors showed higher primary structure homology, lower homology of hormone binding domain, but no homology in primary structure of variable region. The variable domain contains the activated domain, the DNA binding domain, and the zinc finger structure with 4 cysteine residues. The intracellular receptor combines the DNA binding domain with the response element of the corresponding target gene,Two, the mechanism of gene expression regulated by lipid soluble extracellular signaling moleculesFig. 17-21 is a schematic diagram of the mechanism of action of glucocorticoids. Glucocorticoid through the cell membrane into the cells after combined with glucocorticoid receptor, receptor binding hormone activated by activation of the receptor into the nucleus binding glucocorticoid response element (GRE, located within the enhancer) when the hormone receptor complex and enhancer binding after activation of promoter, transcription. The mechanisms underlying other lipid soluble hormones are essentially the same.。
细胞内信号转导系统的结构和功能分析
细胞内信号转导系统的结构和功能分析细胞内信号转导系统（cellular signaling pathway）是指细胞内的一系列复杂的生化反应，通过细胞内的信号传递，在细胞内部生化机制的控制下，将外界信息传输到细胞内部的靶位点来进行生理功能调节。
这个系统对于生物体内的正常生长、发育、维护平衡以及抗病抗压等方面都具有重要的意义。
因此，对于学习和深入研究这个系统的结构和功能有着重要的意义。
1.信号转导系统的分类和作用信号传导系统主要分为内源性和外源性两类。
内源性信号传导系统是指一些生化反应物质，如蛋白质、脂质或核酸等，转移已经刺激了外部的基因，将这些刺激的信息转化为内部信号从而引发细胞内反应的生化途径。
而外源性信号传导系统则是指身体对环境或沟通的一些反应，如例子，抵抗外来病原体菌体的侵袭或细胞内的代谢功能。
这两个系统的共同作用，使人体能够接收身体内外的信息并调节身体的生理状态。
2.信号转导系统的结构信号传导系统主要包括基因、拓扑映射、蛋白质、糖、酸和其他生化反应物质等方面的分子。
这些分子构成了一个庞大的复杂系统，涉及到细胞外受体、嵌合蛋白、激酶等多种蛋白质和其他配合物质的作用与合作。
具体来讲，内源性信号传导系统主要包括如下三个部分：外源性刺激物质―受体―信号传导蛋白。
在整个系统中，以受体和信号传导蛋白为核心，通过细胞内的信号传递，将外界信息转化为细胞内部的反应，进一步调控细胞的生理状态。
不过，在不同类型的信号传导系统中，其中的结构和组成也有所不同。
例如，外源性信号传导系统主要包括细胞膜受体、细胞核受体、细胞内受体和细胞间受体等。
其信号传导方式包括了酶依赖型、酶无依赖型、离子依赖型等多种方式。
3.信号转导系统的作用信号转导系统不仅对人体内部的正常生长、发育有重要影响，同时在人体免疫反应、代谢功能、精神状态等方面也发挥着重要作用。
作为维持人体内正常生物反应对环境的适应之策，信号转导系统具有以下几个重要的作用。
细胞信号转导与免疫系统调节机制
细胞信号转导与免疫系统调节机制在我们的身体内部，存在着一个极其复杂且精妙的防御系统——免疫系统。
它就像是一支训练有素的军队，时刻准备着抵御外来病原体的入侵，同时还要监控和清除体内出现的异常细胞。
而在免疫系统有条不紊地运行过程中，细胞信号转导扮演着至关重要的角色，宛如一条条看不见的“指挥线”，精准地调控着免疫系统的各种反应。
要理解细胞信号转导，我们首先要知道细胞就像一个个小小的“智能工厂”，它们能够感知外界环境的变化，并根据这些变化做出相应的反应。
而细胞信号转导就是细胞接收、处理和传递这些外界信息的过程。
这个过程涉及到一系列复杂的分子机制，包括信号分子的产生、释放、传递、接收以及细胞内的信号转导通路的激活等。
在免疫系统中，细胞之间的交流和信息传递主要通过细胞因子、激素、神经递质等信号分子来实现。
这些信号分子就像是“信使”，它们可以在细胞之间穿梭，将信息从一个细胞传递到另一个细胞。
例如，当病原体入侵人体时，巨噬细胞会释放出一些细胞因子，如白细胞介素-1（IL-1）和肿瘤坏死因子α（TNFα），这些细胞因子可以激活其他免疫细胞，如 T 细胞和 B 细胞，从而启动免疫反应。
当信号分子与细胞表面的受体结合时，就会引发一系列的细胞内信号转导事件。
这些受体就像是细胞表面的“触角”，能够敏锐地感知外界的信号。
常见的受体类型包括离子通道型受体、G 蛋白偶联受体、酶联受体等。
以 G 蛋白偶联受体为例，当信号分子与之结合后，会激活与之偶联的 G 蛋白，进而引发细胞内一系列的生化反应，如激活或抑制某些酶的活性，改变细胞内第二信使（如 cAMP、Ca²⁺等）的浓度，最终导致细胞的生理功能发生改变。
免疫系统的调节机制是一个多层次、多维度的复杂网络，而细胞信号转导在其中发挥着关键的作用。
在免疫细胞的活化过程中，细胞信号转导起着“点火器”的作用。
例如，T 细胞的活化需要两个信号：第一信号是 T 细胞受体（TCR）与抗原提呈细胞表面的抗原肽MHC 复合物结合；第二信号则是由共刺激分子（如CD28 与B7）的相互作用提供。
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信号转导系统信号转导生物体对环境(包括外环境和内环境)信号变化有极高的反应性。
如细菌趋向营养物的运动，视觉细胞对光的感觉，饥饿时激素信号使燃料分子(feul molecules)如糖、脂肪、蛋白质等释放内部能量，生长因子诱导分化等都是典型的例子。
细胞对外界刺激的感受和反应都是通过信号转导系统(signal transduction system)的介导实现的。
该系统由受体、酶、通道和调节蛋白等构成。
通过信号转导系统、细胞能感受、放大和整合各种外界信号。
第一节细胞信号的概况一、细胞外信号分子的识别在多细胞高等生物体内，细胞间的相互影响是通过信号分子实现的，信号分子包括蛋白质、肽、氨基酸、核苷酸、类固醇、脂肪酸衍生物和一些溶于水的气体分子，如一氧化碳、一氧化氮等。
这些信号分子大多数由信号细胞(signaling cells)分泌产生，有些是通过扩散透过细胞膜释放，有些则是和细胞膜紧密结合，需要通过细胞接触才能影响到和信号细胞相接触的其他细胞。
信号分子对靶细胞的作用都是通过一类特异的蛋白质——受体实现的，受体能特异地识别信号分子。
靶细胞上的受体大多数是跨膜蛋白质(transmembrane proteins)，当受体蛋白和细胞外信号分子(也称配体ligand)结合后就被激活，从而启动靶细胞内信号转导系统的级联反应(cascade)。
有些受体位于细胞内，信号分子必须进入细胞才能与受体结合，并使受体激活，这些信号分子都是分子量很小而且是脂溶性的，能扩散通过细胞膜进入细胞。
二、分泌性信号分子作用途径旁分泌(paracrine)由细胞分泌的信号分子只是作为局部的介导物，作用于邻近的靶细胞，称为旁分泌。
旁分泌的信号分子由细胞分泌后，不能扩散至较远的距离，这种信号分子很快地被邻近的靶细胞摄入，或被细胞外酶降解(图17-1A)。
突触(synapses)在较高等的多细胞生物体内，神经细胞(或神经元)能通过轴突与相距较远的靶细胞接触。
当神经细胞在接受来自环境或其他神经细胞的信号而被激活后，就能沿轴突传输电脉冲，脉冲到达轴突末端的神经末梢时，就能刺激末梢分泌神经递质(neurotransmitter)。
神经末梢在化学突触和突触后靶细胞接触并释放神经递质给靶细胞(图17-11B)。
内分泌能分泌激素的信号细胞称为内分泌细胞，内分泌细胞产生的激素进入血液再到达分布于生物体其他部位的靶细胞(图17-1C)。
内分泌信号与突触信号相比，前者因通过血液扩散故速度慢，后者不仅速度快而且精确。
自分泌(autocrine)有一种信号途径是联系同一种细胞，或信号的靶细胞就是产生信号的细胞本身，这叫自分泌。
在生物体发育和分化过程中，一旦某一细胞已定向分化，这个细胞就能分泌自分泌信号分子来增强这种特异的分化过程，因此自分泌信号被认为可能是生物体早期发育阶段以“群落效应”(community effect)为基础的机制。
间隙连接(gap junction)一种能使邻近细胞协同的信号分子作用途径是通过间隙连接。
这种直接使细胞膜连接的通道能使细胞间交换一些小分子的细胞内信号分子，如Ca2+和环腺苷酸(cAMP)等，但大分子信号分子不能通过。
第二节细胞膜受体的类型受体是位于细胞膜或细胞内的一类特殊的蛋白质，可特异地识别信号分子并与之结合，从而启动细胞内信号转导系统的级联反应。
根据在细胞中的位置，受体可以分为细胞膜受体与细胞内受体。
细胞膜受体蛋白占细胞总蛋白质量的比例很小，仅0.01％，因此很难纯化。
由于重组DNA技术的发展，可以对受体蛋白的基因进行克隆，这就极大地促进了对受体蛋白的研究。
细胞膜受体蛋白有三种类型：离子通道偶联受体(ion-channel coupled receptors)、G蛋白偶联受体(G-protein coupled receptors)、酶偶联受体(enzyme coupled receptors)。
膜受体作为信号转导体，能以高亲和力与细胞外的信号分子结合，再将细胞外信号转变为细胞内一个或多个信号，从而改变细胞的生物行为。
一、离子通道偶联受体离子通道偶联受体参与电兴奋细胞间的突触信号快速传递，这类信号由一部分神经递质介导。
神经递质与受体结合后，能改变受体的结构，使离子能通过由受体蛋白构成的通道，进入突触后细胞，改变突触后细胞的兴奋性，如图17-2所示。
二、G蛋白偶联受体G蛋白偶联受体间接地调节其他膜结合的靶蛋白，这些靶蛋白可以是酶或是离子通道。
受体与靶蛋白之间的联系是通过GTP结合调节蛋白(简称G蛋白)实现的。
如果靶蛋白是酶，那么靶蛋白的激活就能改变细胞内与信号转导有关的分子的浓度；如果靶蛋白是离子通道，那么就能改变细胞膜对离子的通透性，如图17-3所示。
三、酶偶联受体酶偶联受体与信号分子结合后，受体蛋白本身就能发挥酶的功能，或激活与受体相关的其他酶蛋白。
这类受体的配体结合部位在细胞外，催化部位在细胞内，如图17-4所示。
这类受体的酶活性主要是蛋白激酶活性，或与蛋白激酶相关的活性，催化靶细胞内与信号转导有关的蛋白质磷酸化。
第三节通过G蛋白偶联受体介导的信号转导系统一、G蛋白偶联受体家族G蛋白偶联受体是一类最大的细胞膜受体家族，在哺乳动物中已发现百余种这类受体。
此家族受体能与许多种信号分子结合，包括激素，神经递质和局部介导物质。
从化学结构上看，信号分子可以是蛋白质、小肽、氨基酸和脂肪酸的衍生物等。
相同的信号分子可以结合和激活此受体家族中的不同成员；例如肾上腺素至少能和9种G蛋白偶联受体结合，并使之激活。
从结构上看，此受体家族成员十分相似，都是只有一条多肽链的跨膜蛋白，跨膜部分由肽链7个不连续的肽段组成，如图17-5所示。
此受体家族从生物进化角度来说，不仅在蛋白质结构上是保守的，而且在功能上也是保守的。
因为无论是在单细胞生物，还是在多细胞生物，它们都能接受细胞外信号，然后再转导给G蛋白。
二、三聚体GTP-结合蛋白(trimeric GTP-binding proteins，G 蛋白)G蛋白是一类与GTP或GDP结合、具有GTP酶活性的位于细胞膜胞质面的膜蛋白，其活性状态取决于结合的是GTP还是GDP。
当与GTP结合时，G蛋白具有活性；与GDP结合时不具活性。
具有活性的G蛋白能激发细胞内信号转导系统的其他成分。
G蛋白可分为两类，一类是作为细胞外信号转导体的三聚体GTP-结合蛋白，一类是在细胞内信号间起作用的单体GTP-结合蛋白(也称单体GTP酶)。
一般将三聚体GTP-结合蛋白简称为G蛋白，由三个不同的亚基组成，分别是α亚基、β亚基、γ亚基。
G蛋白有许多种，常见的有激活腺苷酸环化酶的激动型G蛋白(stimulatory G protein,Gs)、抑制腺苷酸环化酶的抑制型G蛋白(inhibitory G protein,Gi)和激活磷脂酶C-β(phospholipase C-β，一种特异作用于肌醇磷脂的磷脂酶C)的Gq等。
G蛋白同时具有GTP酶活性，水解与G蛋白结合的GTP为GDP，从而使G蛋白失活。
三、第二信使(second messengers)多数G蛋白偶联受体能激活反应链，改变一种或数种细胞内小的信号分子的浓度，通过这些小的信号分子进一步将信号下传，如cAMP、Ca2+、IP3和DG等，通常将这一类在细胞内传递信号的小分子化合物称为第二信使。
cAMP和Ca2+是两种了解比较全面的细胞内信使，在大多数动物细胞中，两种不同的反应途径刺激这两种细胞内信使浓度的改变，大多数G蛋白偶联受体是只调节其中一条信号转导途径，如图17-6所示。
四、通过cAMP的信号转导系统(一)受体通过调节腺苷酸环化酶来控制cAMP浓度作为一种细胞内信使，cAMP浓度的变化相当快，在细胞对激素的反应中，几秒钟内cAMP的浓度变化达5倍以上。
这种快速反应的机制是通过两种酶实现的，腺苷酸环化酶和cAMP磷酸二酯酶。
腺苷酸环化酶的底物是ATP，产物是cAMP，此酶是一种细胞膜结合蛋白。
磷酸二酯酶能快速水解cAMP，产生5’-AMP，如图17-7所示。
细胞外信号主要通过改变腺苷酸环化酶的活性而不是磷酸二酯酶的活性来控制cAMP的水平。
不同的激素和靶细胞膜上的相应受体结合后，有些通过Gs蛋白激活腺苷酸环化酶、升高细胞内cAMP浓度，如促甲状腺素、促肾上腺皮质激素、促黄体生成素、肾上腺素、甲状旁腺素、胰高血糖素、抗利尿激素等；有些通过Gi蛋白抑制腺苷酸环化酶，能降低细胞内cAMP浓度。
α2—肾上腺素能受体与Gi蛋白偶联，β肾上腺素能受体与Gs蛋白偶联，因此肾上腺素和受体结合后通过与不同类型的G蛋白，刺激或抑制腺苷酸环化酶，从而控制细胞内cAMP浓度。
(二)G蛋白偶联受体到腺苷酸环化酶激活的机制在G蛋白介导的信号转导中，一方面G蛋白可以通过GTP酶活性水解GTP为GDP，重新形成不具活性的三聚体G蛋白，使得G蛋白的信号传递及时终止，有利于G蛋白接收下一次信号。
另一方面，当信号分子长期存在时，一类特定的G蛋白偶联受体激酶(G-protein coupled receptor kinases, GRK)使得G蛋白偶联受体羧基端的多个丝氨酸残基发生磷酸化，从而受体与G蛋白介偶联；同时捕获蛋白(arrestin)可以识别并结合磷酸化的受体，阻断受体与G蛋白之间的相互作用。
(三)cAMP依赖的蛋白激酶介导cAMP效应在动物细胞，cAMP主要通过激活cAMP依赖的蛋白激酶(简称蛋白激酶A，protein kinase A, PKA)发挥其生物效应。
PKA催化ATP分子上末端磷酸基团转移到选择性靶蛋白上特异的丝氨酸残基或苏氨酸残基上，被共价磷酸化修饰的氨基酸残基进而调控该靶蛋白的活性。
无活性状态的PKA 具有两个相同的催化亚基和两个相同的调节亚基，调节亚基能结合cAMP。
当cAMP和调节亚基结合后，该亚基的构象发生变化，使调节亚基从酶分子上解离下来，释出的催化亚基激活，催化底物蛋白质分子的磷酸化，如图17-9所示。
肾上腺素与骨骼肌细胞膜上的β-肾上腺素能受体结合后，通过Gs蛋白使细胞内腺苷酸环化酶激活，cAMP浓度升高，cAMP激活PKA，PKA使两种酶磷酸化，一种是磷酸化酶激酶，此酶因磷酸化而被激活并激活糖原磷酸化酶，最后使糖原分解(如图17-10所示)。
另一种被PKA磷酸化的酶是糖原合成酶，该酶因磷酸化而失活。
因此通过这两种酶的作用，即促进糖原分解和抑制糖原合成，使得血糖水平升高。
在有些动物细胞cAMP浓度的提高能激活一些特异基因的转录。
如在能分泌一种叫生长激素释放抑制激素(somatostatin或GHRIH)的细胞中(下丘脑和胰腺δ细胞)，cAMP能使编码该激素的基因开放。
这类基因的调控区有一短序列的顺式元件，称为cAMP反应元件(cAMP response element，CRE)，能识别CRE的转录因子称为CRE结合蛋白，简称CREB。