Receptorfamilies and subfamilies discussed in the text are presented.Abbreviationsused:R,receptor;R,receptor;PDGF,platelet-derived growth factor;SCF,stemcell factor;CSF,colony-stimulationg factor;EGF,epidermal growth factor;FGF,fibroblast growth factor;IGF,insulin- like growth factor:HGF,hepatocytegrowth factor:MSP,macrophage-stimulating protein:VEGF,vascular endothelialgrowth factor;FN,fibronectin;GH,growthhormone;EPO,erythropoietin;PRL,prolactin;IL,interleukin;LIF,leukemia inhibitoryfactor;CNTR,ciliary neurotrophic factore:IFN,interferon:TNF,tumor necrosisfactor:Lngfr,low affinity nerve growth factor rcecptor,TCR,T,cellrcecptor;BCR,B cell rcecptor;receptor;TGFR,transfoming growth factorBAct,activin;BMP,bone morphogenic protein,Alternative desingations are givenwithin parentheses. 单次跨膜受体所介导的信号传递与转换过程与G蛋白偶联型受体介导的信号转导有着很大差别。我们已经知道，G蛋白偶联型受体所介导 的主要是经由G蛋白的激活，然后作用于相应的效应分子，接下来最主要的是导致细胞内信使含量及分布的迅速改变从而调节靶分子的活性并 改变细胞的功能状态。单次跨膜受体介导的信号转导过程则主要是蛋白分子的相互作用，并且有蛋白酪氨酸激酶的广泛参与。对这些信号转导 途径的了解在九十年代中取得了许多重要的进展。为跟踪和理解这些信号转导过程，我们首先需要知道参与这一过程的重要信号转导分子和其 中的一些特殊结构。 1.几类重要的介导单次跨膜受体信号转导的蛋白分子的结构及功能 (1)蛋白激酶 蛋白激酶是指能够将y·磷酸基因从磷酸供体分子上转移至底物蛋白的氨基酸受体上的一大类酶。磷酸供体可以是ATP,也可以是其它类三 磷酸核苷酸。由于蛋白激酶常常是多底物的，因此蛋白激酶是根据底物中氨基酸残基的特异性而不是根据底物蛋白的特异性来分类的。国际生 化学会命名委员会建议将蛋白激酶分为五大类： 激酶 磷酸基团的受体 蛋白丝氨酸/苏烫酸激醉 丝氨酸/苏氨酸羟基 蛋白酪氨酸激确 酪酸的酚羟基 蛋白组/赖/精领酸激酶 咪唑环，胍基，-氨基 蛋白半胱酸激确 疏基 蛋白天冬酸/谷氨酸激确 酰基 前两类激酶目前了解的较多，很多已经获得了cDNA克隆，但对后两者的了解仍很有限。 蛋白丝/苏氨酸激酶和蛋白酪氨酸激酶的分类见表21·5。 表215蛋白激酶分类 1蛋白丝氨酸苏氨酸激确 (1)Cyclic nucleotide regulated A.PKAa cAMP?dependent protein kinase catalytic,a form B.PKA BcAMP?dependent protein kinase catalytic,B form C.PKA yeAMP?dependent protein kinase catalytic,y form D.cGPK?a cGMP?dependent protein kinase a form E.cGPK?B cGMP?dependent protein kinase B form (2)Diacylglycerol regulated:[BH] PKC a protein kinase C a PKCB protein kinase C B PKCy protein kinase Cy PKC8 protein kinase C PKC E protein kinase CE PKC protein kinase C PKC n protein kinase Cn (3)Calcium/calmodulin regulated[BH] CaMl Caleium/calmodulin?dependent protein kinase I CaMlla Calcium/calmodulin?dependent protein kinase lla CaMIIB Calcium/calmodulin?dependent protein kinase IB CaMlly Calcium/calmodulin?dependent protein kinase lly CaMIllCaleium/calmodulin?dependent protein kinase Ill CaMIVCalcium/calmodulin?dependent protein kinase IV PSKHI Putative protein?serine kinase (4)Ribosomal S6 protein kinase S6kI.S6KII,70kDaS6 (5)Serpentine receptor kinase 1B ARK B?Adrenergic receptor protein kinase 2B ARK?related protein kinase ③Rhodopsin kinase (6)Casein kinaseⅡ (7)Glycogen synthase kinase 3 (8)cde 2 family (9)cde 2 related protein kinase (10)MAP kinase(mitogen activated protein kinases) EPK-1,ERK-2,ERK-3,ERK-5(extracellular signal-regulated kinase) JNK(c-Jun N-terminal kinase),P38,etc. (11)MOS/Raf protein kinase 2蛋白酪氨酸激酶 (1)Growth factor receptors EGFR:EGFR.erbB2.erbB3 INSR:INSR,IGF?IR FGFR:FGER.FGER2.c?kit DGFR:PDGFR,CSFIR (2)Non?receptor tyrosine kinase sre family:sre,Yes,Lyn,Fyn,Lck,etc Syk family:Syk,ZAP70Receptorfamilies and subfamilies discussed in the text are presented .Abbreviationsused: R, receptor; R, receptor; PDGF,platelet-derived growth factor; SCF, stemcell factor; CSF, colony-stimulationg factor; EGF,epidermal growth factor; FGF,fibroblast growth factor; IGF, insulin￾like growth factor;HGF, hepatocytegrowth factor;MSP,macrophage-stimulating protein;VEGF,vascular endothelialgrowth factor;FN,fibronectin;GH,growthhormone;EPO,erythropoietin;PRL,prolactin;IL,interleukin;LIF,leukemia inhibitoryfactor;CNTR,ciliary neurotrophic factore;IFN,interferon;TNF,tumor necrosisfactor;Lngfr,low affinity nerve growth factor rcecptor;TCR,T ,cellrcecptor;BCR,B cell rcecptor;receptor;TGFR,transfoming growth factorβAct,activin;BMP,bone morphogenic protein,Alternative desingations are givenwithin parentheses. 单次跨膜受体所介导的信号传递与转换过程与G蛋白偶联型受体介导的信号转导有着很大差别。我们已经知道，G蛋白偶联型受体所介导 的主要是经由G蛋白的激活，然后作用于相应的效应分子，接下来最主要的是导致细胞内信使含量及分布的迅速改变从而调节靶分子的活性并 改变细胞的功能状态。单次跨膜受体介导的信号转导过程则主要是蛋白分子的相互作用，并且有蛋白酪氨酸激酶的广泛参与。对这些信号转导 途径的了解在九十年代中取得了许多重要的进展。为跟踪和理解这些信号转导过程，我们首先需要知道参与这一过程的重要信号转导分子和其 中的一些特殊结构。 1.几类重要的介导单次跨膜受体信号转导的蛋白分子的结构及功能 (1)蛋白激酶 蛋白激酶是指能够将γ－磷酸基因从磷酸供体分子上转移至底物蛋白的氨基酸受体上的一大类酶。磷酸供体可以是ATP，也可以是其它类三 磷酸核苷酸。由于蛋白激酶常常是多底物的，因此蛋白激酶是根据底物中氨基酸残基的特异性而不是根据底物蛋白的特异性来分类的。国际生 化学会命名委员会建议将蛋白激酶分为五大类： 激 酶 磷酸基团的受体 蛋白丝氨酸／苏氨酸激酶 丝氨酸／苏氨酸羟基 蛋白酪氨酸激酶 酪氨酸的酚羟基 蛋白组／赖／精氨酸激酶 咪唑环，胍基，ε－氨基 蛋白半胱氨酸激酶 巯基 蛋白天冬氨酸／谷氨酸激酶 酰基 前两类激酶目前了解的较多，很多已经获得了cDNA克隆，但对后两者的了解仍很有限。 蛋白丝/苏氨酸激酶和蛋白酪氨酸激酶的分类见表21－5。 表21-5 蛋白激酶分类 1.蛋白丝氨酸/苏氨酸激酶 (1) Cyclic nucleotide regulated A. PKA α cAMP?dependent protein kinase catalytic,α form B. PKA βcAMP?dependent protein kinase catalytic, β form C. PKA γcAMP?dependent protein kinase catalytic,γ form D. cGPK?α cGMP?dependent protein kinase α form E. cGPK?β cGMP?dependent protein kinase β form (2) Diacylglycerol regulated:[BH] PKC α protein kinase C α PKC β protein kinase C β PKC γ protein kinase C γ PKC δ protein kinase C δ PKC ε protein kinase C ε PKC ζ protein kinase C ζ PKC η protein kinase C η (3)Calcium/calmodulin regulated[BH] CaMⅠ Calcium/calmodulin?dependent protein kinase Ⅰ CaMⅡα Calcium/calmodulin?dependent protein kinase Ⅱα CaMⅡβ Calcium/calmodulin?dependent protein kinase Ⅱβ CaMⅡγ Calcium/calmodulin?dependent protein kinase Ⅱγ CaMⅢCalcium/calmodulin?dependent protein kinase Ⅲ CaMⅣCalcium/calmodulin?dependent protein kinase Ⅳ PSKHI Putative protein?serine kinase (4) Ribosomal S6 protein kinase S6kⅠ,S6KⅡ,70kDaS6 (5) Serpentine receptor kinase ① β ARK β?Adrenergic receptor protein kinase ② β ARK?related protein kinase ③ Rhodopsin kinase (6) Casein kinase Ⅱ (7) Glycogen synthase kinase 3 (8) cdc 2 family (9) cdc 2 related protein kinase (10)MAP kinase (mitogen activated protein kinases) EPK－1, ERK－2, ERK－3, ERK－5(extracellular signal－regulated kinase) JNK(c－Jun N－terminal kinase), P38, etc. (11)MOS/Raf protein kinase 2.蛋白酪氨酸激酶 (1) Growth factor receptors EGFR: EGFR.erbB2,erbB3 INSR:INSR, IGF?1R FGFR:FGFR, FGFR2, c?kit DGFR:PDGFR, CSFIR (2) Non?receptor tyrosine kinase src family: src,Yes,Lyn,Fyn,Lck,etc Syk family:Syk, ZAP70