MetabolickinasesmoonlightingasproteinkinasesZhiminLu1,2,3andTonyHunter41BrainTumorCenterandDepartmentofNeuro-Oncology,TheUniversityofTexasMDAndersonCancerCenter,Houston,TX77030,USA2DepartmentofMolecularandCellularOncology,TheUniversityofTexasMDAndersonCancerCenter,Houston,TX77030,USA3CancerBiologyProgram,TheUniversityofTexasGraduateSchoolofBiomedicalSciencesatHouston,Houston,TX77030,USA4CancerBiologyProgram,MDAndersonCancerCenterUTHealthGraduateSchoolofBiomedicalSciences,TheUniversityofTexas,Houston,Texas77030,USAAbstractProteinkinasesregulateeveryaspectofcellularactivity,whereasmetabolicenzymesareresponsibleforenergyproductionandcatabolicandanabolicprocesses.Emergingevidencedemonstratesthatsomemetabolicenzymes,suchaspyruvatekinaseM2,phosphoglyceratekinase1,ketohexokinaseisoformA,hexokinase(HK),andnucleosidediphosphatekinase1and2(NME1/2),thatphosphorylatesolublemetabolitescanalsofunctionasproteinkinasesandphosphorylateavarietyofproteinsubstratestoregulatetheWarburgeffect,geneexpression,cellcycleprogressionandproliferation,apoptosis,autophagy,exosomesecretion,T-cellactivation,irontransport,ionchannelopening,andmanyotherfundamentalcellularfunctions.Theelevatedproteinkinasefunctionsofthesemoonlightingmetabolicenzymesintumordevelopmentmakethempromisingtherapeutictargetsforcancer.Keywordsmetabolicenzymes;proteinkinase;phosphorylationProteinkinasesareimportantregulatorsofintracellularsignaltransductionpathwaysthatmediatethedevelopmentandregulationofbothunicellularandmulticellularorganisms.Theyplaycriticalrolesincellgrowth,division,differentiation,adhesion,motility,anddeath(BrognardandHunter,2011;LuandHunter,2009).Theseproteinkinases,morethan500ofwhichexistinthehumangenome,canbeprimarilysubdividedintotyrosine(Y)-andserine(S)/threonine(T)-specifickinasesbasedontheircatalyticspecificity(Manningetal.,2002).Correspondence:ZhiminLuaandTonyHunterb,aTel:713-834-6231;Fax:713-834-6230,zhiminlu@mdanderson.org.bTel:858-453-4100;Fax:858-457-4765,hunter@salk.edu.Publisher'sDisclaime...
