Fibroblastgrowthfactors(FGFs)compriseafamilyofatleast23structurallyrelatedproteinsthatareinvolvedinamultitudeofphysiologicalandpathologicalcellularprocessesincluding:cellgrowth,proliferationanddifferentiation,angiogenesis,chemotaxis,apoptosis,woundhealingandtumOrigenesis(1,2).TheBIOLOGicalactivitiesoftheFGFsaremediatedbyafamilyoftypeItransmembranetyrosinekinases(3).FourdistinctgenesencodingcloselyrelatedFGFreceptors,FGFR1-4,havebeenidentified(4).TheFGFRshaveseveralalternativelysplicedisoformsthatexhibitvariABIlityinligandaffinity,expressionpatterns,andsignalingproperties(5-10).
HeparinorheparinsulfateproteoglycansareimportantcofactorsmediatingtheinteractionofFGFwithFGFRs(11-14).BindingofFGFtoFGFR3,resultsinreceptordimerization,followedbytrans-autophosphorylationofseveraltyrosineresiduesinthetyrosinekinasedomain(7,12,15).Structurally,theextracellularportionofFGFR3containsthreeimmunoglobulin(Ig)domains;thefirsttwoareseparatedbyastretchofacidicaminoacidstermedtheacidbox(3).FGFR3containsasingletransmembranedomainanddualintracellulartyrosinekinasedomains(3).
Duringhumandevelopment,FGFR3expressionisenrichedinbrain,lungintestine,kidney,skin,growthplate,andcalvarialbone(16).PointmutationsinFGFR3havebeendescribedforseveralskeletaldisorders,includinghypochondroplasia(17),thanatophoricdysplasia(18),SADDAN(severeachondroplasiawithdevelopmentaldelayandacanthosisnigricans)(19),craniosynostosis(20)andCrouzonsyndromewithacanthosisnigricans(21).Consistentwitharoleinskeletaldevelopment,morethan97%ofindividualswithachondroplasia,themostcommonformofdwarfism,exhibitaGly380ArgactivatingmutationintheFGFR3transmembranedomain(22).Aswithmanyothergrowthfactorreceptors,activatingmutationsinFGFR3canbeoncogenic(23).Forexample,FGFR3mutationshavebeenidentifiedincolorectal(24),andbladder(25)cancers.Inaddition,about20%ofmultiplemyelomacasesandderivedcelllinesexhibitachromosomaltranslocationeventthatresultsintheexpressionofFGFR3ontheplasmacellsurface(26-28).ThecomplexpatternsofexpressionoftheFGFRsaswellasthespecificityoftheirinteractionswiththevariousFGFligandfamilymembersareactiveareasofinvestigation.
1.Ornitz,D.M.andN.Itoh(2001)GenomeBiol.2:3005.1
2.Powers,C.J.etal.(2000)Endocrin.Relat.Cancer7:165.
3.Keegan,K.etal.(1991)Proc.Natl.Acad.Sci.USA88:1095.
4.Johnson,D.E.andL.T.Williams(1993)Adv.CancerRes.60:1.
5.Murgue,B.etal.(1994)CancerRes.54:5206.
6.Chellaiah,A.T.etal.(1994)J.Biol.Chem.269:11620.
7.Kanai,M.etal.(1997)J.Biol.Chem.272:6621.
8.Shimizu,A.etal.(2001)J.Biol.Chem.276:11031.
9.Shimizu,A.etal.(2002)Biochem.Biophys.Res.Commun.290:113.
10.Jang,J-H.(2002)Biochem.Biophys.Res.Commun.292:378.
11.Rapraeger,A.C.etal.(1991)Science252:1705.
12.Spivsk-Kroizman,T.etal.(1994)Cell79:1015.
13.Ornitz,D.M.etal.(2000)Bioessays22:108.
14.Lin,X.etal.(1999)Development126:3715.
15.Hart,K.C.etal.(2001)Mol.Biol.Cell12:931.
16.Partanen,J.etal.(1991)EMBOJ.10:1347.
17.Bellus,G.A.etal.(1995)Nat.Genet.10:357.
18.Tavormina,P.L.etal.(1995)Nat.Genet.9:321.
19.Bellus,G.A.etal.(1999)Am.J.Med.Genet.85:53.
20.Muenke,M.etal.(1997)Am.J.Hum.Genet.60:555.
21.Meyers,G.A.etal.(1995)Nat.Genet.11:462.
22.Bellus,G.A.etal.(1995)Am.J.Med.Genet.56:368.
23.Chesi,M.etal.(2001)Blood97:729.
24.Jang,J-H.(2001)CancerRes.61:3541.
25.Capellan,D.etal.(1999)Nat.Genet.23:18.
26.Zhan,F.etal.(2002)Blood99:1745.
27.Chesi,M.etal.(1998)Blood92:3025.
28.Richelda,R.etal.(1997)Blood90:4062.
Neuromics公司提供一系列高品质新蛋白的抗体、神经干细胞及培养基、神经干细胞扩增及分化试剂盒、干细胞抗体、神经和前体细胞流式分型试剂、细胞凋亡研究试剂、荧光激活细胞分拣法试剂盒、细胞内部试剂盒、转染试剂、ELISA 缓冲稀释液与IHC-WB-ELISA 补充物等试剂。
Neuromics因为是由一批顶尖的学术和商业实验室挑选,试验和创新他们的 试剂来满足顾客的需要而使自己的表现尤为突出。Neuromics从 以上过程中获得的经验使得顾客****的实际应用和试剂独特的性能能够得以相容。它精通于提供试剂和为神经科学研究机构提供产品和服务。