Testing and Thinkingl. (True/False) There is no fundamentaldistinction betweensignaling molecules that bind to cell-surface receptors andthose that bind to intracellular receptors. Explain youranswer.2. How is it that different cells can respond in different waysto exactly the same signaling molecule even when they haveidenticalreceptors?3. Why do you suppose that别构或变构phosphorylation/dephosphorylation, as opposed to allostericbinding of small molecules,for example,plays such aprominent role in switching proteins on and off in signalingpathways?
1 Testing and Thinking 1. (True/False) There is no fundamental distinction between signaling molecules that bind to cell-surface receptors and those that bind to intracellular receptors. Explain your answer. 2. How is it that different cells can respond in different ways to exactly the same signaling molecule even when they have identical receptors? 3. Why do you suppose that phosphorylation/dephosphorylation, as opposed to allosteric binding of small molecules, for example, plays such a prominent role in switching proteins on and off in signaling pathways? 别构或变构
Testing and Thinking1.Thehormoneglucagon（胰高血糖素）stimulatesthebreakdownofstoredglycogen（糖原）in liver and muscle cells by the followingenzymes.Whichis the first enzyme that must be activated?(a.Protein kinaseAb.Phosphorylasekinased.Protein phosphatasec.Glycogenphosphorylasee.Proteinphosphataseinhibitor-l2.Fillin the blanks with the appropriateterms:isanintracellularproteinthatbinds calciumand activates(a)enzymes.(b)A substance that fits intoa specificbinding site on the surface of aproteinmoleculeis calleda2
2 Testing and Thinking 1. The hormone glucagon（胰高血糖素） stimulates the breakdown of stored glycogen（糖原） in liver and muscle cells by the following enzymes. Which is the first enzyme that must be activated? ( ) a. Protein kinase A b. Phosphorylase kinase c. Glycogen phosphorylase d. Protein phosphatase e. Protein phosphatase inhibitor-1 2. Fill in the blanks with the appropriate terms: (a) is an intracellular protein that binds calcium and activates enzymes. (b) A substance that fits into a specific binding site on the surface of a protein molecule is called a
ANSWER1.A2.(a) calmodulin (b) ligand3
3 ANSWER 1.A 2.(a) calmodulin (b) ligand
第4节酶联受体信号传递途径Signalingviaenzyme-linked receptor★特点：不需要信号偶联蛋白（G-蛋白），而是通过受体自身的酪氨酸蛋白激酶的活性来完成信号跨膜转换；该通路对信号的反应比较慢（通常要几小时）并且需要许多细胞内的转换步骤；通常与细胞分裂相关
4 第4节 酶联受体信号传递途径 Signaling via enzyme-linked receptor 特点： ◆不需要信号偶联蛋白(G-蛋白), 而是通过受体自 身的酪氨酸蛋白激酶的活性来完成信号跨膜转 换； ◆该通路对信号的反应比较慢(通常要几小时)， 并且需要许多细胞内的转换步骤； ◆通常与细胞分裂相关
enzyme linked receptor、分为两种情况：一本身具有激酶活性，如EGF，PDGF，CSF等的受体；一本身没有酶活性，但可以连接激酶（非受体酪氨酸)，如细胞因子受体超家族。5
5 • 分为两种情况： – 本身具有激酶活性，如EGF，PDGF，CSF等的受 体； – 本身没有酶活性，但可以连接激酶(非受体酪氨 酸)，如细胞因子受体超家族。 enzyme linked receptor
酶偶联受体的种类已知5类分开）·酪氨酸激酶偶联受体(tyrosinekinase-linkedreceptors)：·受体鸟苷环化酶（Receptorguanylylcyclase）；受体酪氨酸磷酸酶(Receptoroftyrosinephophatase);受体酪氨酸激酶母(Receptortyrosinekinase);·受体丝氨酸/苏氨酸激酶母 (Receptor serine/threoninekinase)。6
6 酶偶联受体的种类 ●酪氨酸激酶偶联受体(tyrosine kinase-linked receptors): ●受体鸟苷环化酶 (Receptor guanylyl cyclase)； ●受体酪氨酸磷酸酶 (Receptor of tyrosine phophatase); ●受体酪氨酸激酶 (Receptor tyrosine kinase)； ●受体丝氨酸/苏氨酸激酶 (Receptor serine/threonine kinase)。 已知5类 分开
酶联受体结构与配体结合的细胞外结构域：单次跨膜结构域膜内部分有酶活性或与酶相连的结构域：7
7 酶联受体结构 ◆与配体结合的细胞外结构域； ◆单次跨膜结构域。 ◆膜内部分有酶活性或与酶相连的结构域；
Inactivemonomers酶偶联型受体的共同点：①单次跨膜蛋白：Activedimersoeo②接受配体后发生二聚化，起动下游信号转导。Transautophos-phorylationSignaltransmissionSH2-SH2domaindomainAfterJ.SchiontandA.Uirich,Neuwon 8:384,1992:bypermistionofCellPreusCopyrignt1999 John Wiey and Sons,inc.All rightsreserved
8 酶偶联型受体的共同点： ①单次跨膜蛋白； ②接受配体后发生二聚化， 起动下游信号转导
受体酪氨酸激酶Ras信号途径受体酪氨酸激酶，简称RTKs(receptortyrosinekinase)是最大的一类酶联受体Ras是原癌基因c-ras表达的产物，RTKs/Ras是目前研究得比较清楚的一条主要的信号转导途径原癌基因是细胞的正常基因，其表达产物对细胞的生理功能极其重要只有当原癌基因发生结构改变或过度表达时，才可能导致细胞癌变
9 受体酪氨酸激酶/Ras信号途径 受体酪氨酸激酶，简称RTKs(receptor tyrosine kinase)是最大的一类酶联受体 Ras是原癌基因c-ras表达的产物，RTKs/Ras是目 前研究得比较清楚的一条主要的信号转导途径。 原癌基因是细胞的正常基因，其表达产物对细胞的生理功能极其重要， 只有当原癌基因发生结构改变或过度表达时，才可能导致细胞癌变
受体酪氨酸激酶(Receptortyrosinekinase)酪氨酸激酶①胞质酪氨酸激酶：如Src、Tec、ZAP70、JAK;②核内酪氨酸激酶：如：Abl、Wee;③受体酪氨酸激酶（RTKs）：为单次跨膜蛋白，配体（如EGF)与受体结合。导致二聚化，二聚体内彼此相互磷酸类型：化胞内段酪氨酸残基表皮生长因子受体（EpidermalEGF);growthfactor,10胰岛素受体（insulinreceptor）
10 受体酪氨酸激酶(Receptor tyrosine kinase) 酪氨酸激酶 ①胞质酪氨酸激酶：如Src、Tec、ZAP70、JAK； ②核内酪氨酸激酶：如：Abl、Wee； ③受体酪氨酸激酶（RTKs） ：为单次跨膜蛋白，配体（如 EGF） 与受体结合。导致二聚化，二聚体内彼此相互磷酸 化胞内段酪氨酸残基。 ◆类型： ●表皮生长因子受体(Epidermal growthfactor, EGF); ●胰岛素受体(insulin receptor)