单次跨膜受体及其信号转导

 

 

多种生长因子和细胞因子的受体为一类结构上为单次跨膜的糖蛋白。与七次跨膜受体(G蛋白偶联型受体)相对应，将其称为单次跨膜受体，即它们的跨膜区仅为单向一次性的，而不像七次跨膜受体那样有反复的跨膜区段。

单次跨膜受体依照其结构特点可进一步分成多个家族和亚家族，其分类见表21－4及图21-7。�

图21－17　各类单次跨膜受体的代表性举例

Receptor Type	Family	Examples	Characteristics
Protein-tyosine kinase receptors	PDGF receptor	PDGFR-α,PDGFR-βSCFR	Five immunoglobulin-like
family	(Kit),CSF-R(Fms),Flk-2	domains extracellularly
EGF receptor family	EGFR(ErbB),ErbB2(Neu),ErbB3,ErbB4	Two cysteine-rich
IGF receptor family	insulin R,IGF-1R	domains extracllularly
HGF receptor family	HGFR(Met),MSPR(Ron)	Disulphide-bound heteroteramer of a and βchain
VEGF receptor family	Flt-1,Flk-1(KDR)	Seven immunolobulin-like domains extracellularly
Neurotrophin receptor family	Trk,TrkB,TrkC
Eph receptor family	Eph ,E1k,Eck,Cck5,Sek,Erk	Two FNIII-like domains and a cysteinerichdomain extracellularly
Cytokine receptors	Class 1 cytokine receptor family
CH receptor subfamily	GHR,EPOR,PRLR,G-CSFR	Form homodimers
IL-3 receptor subfamily	IL-3R,GM-CSFR,IL-5R	Form complexes with the cβ subunit
IL-6 receptor subfamily	IL-6R,LIFR,CNTFR,IL-11R	Form complexs with gp 130
IL-2receptor subfamily	IL-2R,IL-2Rβ,IL-4R,IL-7R	Form complexes with il-2Rγ
	IFN-α/βR,IFN-γRα,IFN-γRβIL-10R
TNF receptor family		TNFR-1,TNFR-11MLNGFR,CD40,OX-40,Fas,CD27,CD30	Form trimers
Antigen receptors		TCR	Complex of α,β,γ,δ,ε,ζandηsubunits
	BCR	Complex of IgM and heterodimers ofα/βsubunits
Serine/threonine kinase receptor family	Type Ⅱ receptor family	TGFβR-Ⅱ,ActR-Ⅱ,ActR-ⅡB	Form hetero-oligomers with type Ireceptors,i, e,TGFβ-I,ActR-1,ActR-1B,BMPR-1A,BMPR-1B,ALK-1

Receptor families and subfamilies discussed in the text are presented .Abbreviations used: R, receptor; R, receptor; PDGF,platelet-derived growth factor; SCF, stem cell factor; CSF, colony-stimulationg factor; EGF,epidermal growth factor; FGF, fibroblast growth factor; IGF, insulin-like growth factor;HGF, hepatocyte growth factor;MSP,macrophage-stimulating protein;VEGF,vascular endothelial growth factor;FN,fibronectin; GH,growth hormone; EPO, erythropoietin; PRL, prolactin; IL, interleukin; LIF, leukemia inhibitory factor; CNTR, ciliary neurotrophic factore;IFN,interferon;TNF,tumor necrosis factor;Lngfr,low affinity nerve growth factor rcecptor;TCR,T ,cell rcecptor;BCR,B cell rcecptor;receptor;TGFR,transfoming growth factor βAct,activin;BMP,bone morphogenic protein,Alternative desingations are given within 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。