
INFORMATION: Human CD66b (CEACAM8, CGMb, NCA-95, CD67) is a 95kD member of the Carcinoembryonic Antigen (CEA) group. It is expressed on granulocytes and functions as an adhesion molecule. Similar to the CD66 a, c, and d isoforms, engagement of CD66b on neutrophils causes increased adhesion to endothelial cells (2). Crosslinking CD66b on neutrophils with antibodies triggers IL-8 release (3).
References:
1) W.N. Khan, S. Hammarstrom, et al. (1992) Genomics 14(2):384-90.
2) K.M. Skubitz, A.P. Skubitz, et al. (1996) J Leuk Biol 60(1): 106-117.
3) A.K. Schroder, L Rink, et al. (2006) Human Immunol 67(9): 676-682.
Antibody from clone ANC4A4 binds to CD66b on the cell surface of humanPMN in Flow cytometry and works as an EIA capture reagent forrecombinant CD66b utilizing either clone ANC1D5(Cat #217-030) orANC3C5(Cat# 219-030) as a detection reagent.
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QianWang,JessamyTiffen,CharlesG.Bailey,MelanieL.Lehman,WilliamRitchie,LadanFazli,CynthiaMetierre,Yue(Julie)Feng,EstelleLi,MartinGleave,GrantBuchanan,ColleenC.Nelson,JohnE.J.Rasko,JeffHolst
Correspondenceto:JeffHolst,PhD,OriginsofCancerLaboratory,LockedBag6,Newtown,NSW2042Australia.(e-mail:j.holst@centenary.org.au).
BackgroundL-typeaminoacidtransporters(LATs)uptakeneutralaminoacidsincludingL-leucineintocells,stimulatingmammaliantargetofrapamycincomplex1signalingandproteinsynthesis.LAT1andLAT3areoverexpressedatdifferentstagesofprostatecancer,andtheyareresponsIBLeforincreasingnutrientsandstimulatingcellgrowth.
MethodsWeexaminedLAT3proteinexpressioninhumanprostatecancertissuemicroarrays.LATfunctionwasinhibitedusingaleucineanalog(BCH)inandrogen-dependentand-independentenvironments,withgeneexpressionanalyzedbymicroarray.APC-3xenograftmousemodelwasusedtostudytheeffectsofinhibitingLAT1andLAT3expression.ResultswereanalyzedwiththeMann-WhitneyUorFisherexacttests.Allstatisticaltestsweretwo-sided.
ResultsLAT3proteinwasexpressedatallstagesofprostatecancer,withastatisticallysignificantdecreaseinexpressionafter4–7monthsofneoadjuvanthormonetherapy(4–7monthmean=1.571;95%confidenceinterval=1.155to1.987vs0month=2.098;95%confidenceinterval=1.962to2.235;P=.0187).InhibitionofLATfunctionledtoactivatingtranscriptionfactor4–mediatedupregulationofaminoacidtransportersincludingASCT1,ASCT2,and4F2hc,allofwhichwerealsoregulatedviatheandrogenreceptor.LATinhibitionsuppressedM-phasecellcyclegenesregulatedbyE2Ffamilytranscriptionfactorsincludingcriticalcastration-resistantprostatecancerregulatorygenesUBE2C,CDC20,andCDK1.InsilicoanalysisofBCH-downregulatedgenesshowedthat90.9%arestatisticallysignificantlyupregulatedinmetastaticcastration-resistantprostatecancer.Finally,LAT1orLAT3knockdowninxenograftsinhibitedtumorgrowth,cellcycleprogression,andspontaneousmetastasisinvivo.
ConclusionInhibitionofLATtransportersmayprovideanoveltherapeutictargetinmetastaticcastration-resistantprostatecancer,viasuppressionofmammaliantargetofrapamycincomplex1activityandM-phasecellcyclegenes.
L-typeaminoacidtransporters(LATs)supplycellswithlargeneutralaminoacids,whicharenotonlyrequiredforproteinsynthesisbutalsocontributetovarioussignalingpathways.Intracellularleucinelevelsaresensedbytheleucyl-transferRNAsynthetase,previouslyknowntocatalyzetheadenosinetriphosphate–dependentligationofL-leucinetotransferRNAduringproteinsynthesis(1,2).Leucyl-transferRNAsynthetaseactivatestheRagguanosinetriphosphatasecomplexandbindstoRaptortoactivatemammaliantargetofrapamycincomplex1(mTORC1)signalingonthesurfaceoflysosomes(1–3).Inthiswayleucineisnotonlyanessentialaminoacidbutactsasarate-limitingsignalingmoleculeinthemTORC1pathway.
Incellsdeprivedofaminoacids,thereisanaccumulationofunchargedtransferRNA,whichbindstoandactivatesthegeneralcontrolnonrepressed2(GCN2)kinase.Inturn,GCN2phosphorylatesthetranslationinitiationfactor2α(eIF2α)onserine51,triggeringtranslationalupregulationofactivatingtranscriptionfactor(ATF)4(4).ATF4itselfupregulatestheexpressionofaminoacidtransportersasameansofrestoringintracellularaminoacidlevels(5).Therefore,understandinghowaminoacidtransportersregulateintracellularleucinelevels,andgeneratingnovelinhibitorsofthesetransporters,mayleadtopotentsuppressorsofmTORC1signaling.
ThetwodistinctfamiliesofLATsare1)solutecarrier7(SLC7)members(LAT1/SLC7A5andLAT2/SLC7A8),whichmediateNa+-independentneutralaminoacidexchangeasheterodimerswiththe4F2cell-surfaceantigenheavychain(4F2hc/SLC3A2/CD98)glycoprotein(6,7);and2)SLC43proteins(LAT3/SLC43A1andLAT4/SLC43A2)thatmediateNa+-independentuniportofneutralaminoacids(8,9).AlthoughtheexpressionofeachLATmembervariesdramaticallyindifferenttissues,thesetransportersarecommonlyupregulatedincancer.IncreasedLAT1expressionhasbeendetectedinlungcancer,coloncancer,breastcancer,headandneckcancer,genitalcancers,andsofttissuesarcomas(10–12).WeandothershaveshownthatLAT1andLAT3areoverexpressedinprostatecancer(11–14),withLAT1expressionincreasedinmetastasiscomparedwithprimarycancer(10,12).
WehypothesizedthatinhibitionofLAT1andLAT3mayofferaneffectivetherapeuticapproachforprostatecancer.
感觉这样的提问是没有意义的
还是自己找下资料吧
微生物吸收营养和排出废弃物都需要通过细胞膜。而细胞膜是磷脂双分子层结构,无论是亲水物质还是疏水物质都无法通过细胞膜。
细胞膜上镶嵌有蛋白质,叫转运蛋白。蛋白质既有疏水基团,又有亲水基团,正是靠蛋白质的这种特殊结构,能够与两类物质结合,并通过蛋白质结构的细微变化,把这两类物质运送到细胞膜的另一侧。
所以,微生物吸收营养物质必须用镶嵌在细胞膜上的转运蛋白来实现。
另外在八版生理248页第二段,近端小管后半段氯离子通过氯离子碳酸氢根交换体被重吸收,此时小管液中氯离子浓度大于周围组织液氯离子浓度,所以也有细胞旁途径顺浓度被动重吸收,然而资料上的总结和题目里都是说氯离子在近端小管的重吸收为被动重吸收,感觉有些糊涂。希望来个大神指点一二。

