CD38是一个定位于膜上的糖蛋白,催化环腺苷二磷酸核糖(cADPR,cyclicADP-ribose)的合成和降解。cADPR是核苷酸的代谢产物,通过作用于ryanodine受体(RyRs)参与细胞内钙库的钙动员。许多研究发现CD38/CADPR介导的Ca2+信号传递和通过RyRs通道的Ca2+释放在Ca2+内平衡的调控中发挥了重要的作用。CD38/CADPR/RyRs介导的Ca2+信号传递也参与了许多病理和生理过程。本文就CD38基因的结构、表达、调控及在心血管系统的功能做一综述。cd38基因包括了8个外显子,5’UTR无TATA盒或CAAT盒(NataK,TakamuraT,KarasawaT,KumagaiT,HashiokaW,TohgoA,YonekuraH,TakasawaS,NakamuraS,andOkamotoH.HumangeneencodingCD38(ADP-ribosylcyclase/cyclicADP-ribosehydrolase):organization,nucleotidesequenceandalternativesplicing.Gene186:285-292,1997.)。一段高GC含量区可能是cd38的启动子区,调节CD38的表达。CD38是一个45kDa的单链跨膜糖蛋白,整体结构分为N末端短的胞质尾,单次跨膜域和C端长的胞外区(图1)。其开放阅读框含有300个氨基酸残基,5ZUTR比较短小,69bp;3ZUTR含有260bp,不包括PolyA尾。其编码的多肽链分子量为34,288道尔顿。天然的CD38抗原的分子量为46,000道尔顿。预测的氨基酸序列没有N-末端的引导肽序列,但在从翻译起始位点起21个氨基酸残基处含有一段长23个氨基酸残基的内部疏水序列。CD38原始序列的亲水性图提示CD38分子仅跨膜一次,也就是说多肽链的长C-末端指向胞外,N-末端有19aa的短胞质尾。(pDavidG.Jackson,JohnI.Bell,IsolationofacDNAencodingthehumanCD38(T10)molecule,acellsurfaceglycoproteinwithanunusualdiscontinuouspatternofexpressionduringlymphocytedifferentiation.TheJournalofImmunology,1990144(7)2811-2815)人类、大鼠和小鼠CD38基因的cDNA已被克隆(Jackson,.,andBell,J.I.(1990)IsolationofaeDNAencodingthehumanCD38(T10)molecule,acellsurfaceglycoproteinwithanunusualdiscontinuouspatternofexpressionduringlymphocytedifferentiation.J.Immunol.144,2811-2817;Harada,N.,Santos-Argumedo,L.,Chang,R.,Grimaldi,C.J.,Lund,F.E.,Brannan,C.DomaiI.,Copeland,N.G.,Jenkins,N.A.,Heath,A.W.,Parkhouse,R.M.,andHoward,M.(1993)ExpressioncloningofaeDNAencodinganovelmurineBcellactivationmarker:homologytohumanCD38.J.,3111-3118;Koguma,T.,Takasawa,S.,Tohgo,A.,Karasawa,T.,Furuya,Y.,Yonekura,H.,andOkamoto,H.(1994)CloningandcharacterizationofeDNAencodingratADP-ribosylcyclase/cyclicADPribosehydrolasefromisletsofLangerbans.Biochim.Biophys.Acta1223,160-162),三种来源的CD38蛋白的氨基酸序列表现出了高的同源性(表1)。由于CD38的蛋白具有N端在胞内,C端在胞外这种结构上的特点,因此属于II型膜蛋白。CD38蛋白胞外部分近C-末端有4个潜在的N-连接糖基化位点,2—4个含有唾液酸的高甘露糖N-连接寡糖链,占其蛋白分子量的25%,还有一个可能的透明质酸结合基序在其胞外域。运用体细胞遗传学方法将人CD38蛋白的编码基因定位在4号染色体(Katz,F.,Povey,S.,Parkar,M.,Schneider,C.,Sutherland,R.,Stanley,K.,Solomon,E.,andCreavesM.(1983)Chromosomeassignmentofmonoclonalantibody-defineddeterminantonhumanleukemiccells.Eur.J.,1008-1013)。随后被进一步定位到4p15(Nakagawara,K.,Mori.M.,Takasawa,S.,Nata,K.,Takamura,I.,Berlova,A.,Tohgo,A.,Karasawa,T.,Yonekura,H.,Takeuchi,T.,andOkamoto,H.(1995)AssignmentofCD38,thegeneencodinghumanleukocyteantigenCD38(ADP-ribosylcyclase/cyclicADPrihosehydrolase),tochromosome4p15.Cyogene:.Cell.Genet.69,38-39)。CD38在鼠类中的同源基因位于5号染色体。与HOX7(),KIT(4p12)等基因成簇分布人类的4号染色体和小鼠的5号染色体上。NHFigure1.SchcnuiicrepmcnuitionofCD38图1CD38结构示意图表1CD38FunctionEffectorta)ExtracellularTrans*CytoplasmicmembraneActNabonandadhesionFleanltmenlassociationand/orwith*Tandactivationc#klnaw(?)AgontaticmAbftSubatfaW(NAD*}andcaH-*B8Gtiaiedc...