Studies on insulin/IGF-1 hybrid and IGF-1 growth-promoting functional region.

Summary Single-chaininsulin/IGF-1hybrid – [ Ins/IGF-1(C) ] ,single-chainporcineinsulinprecursor – (PIP),andB10AspPIPwerepreparedbyproteinengineering.Theirgrowth-promotingactivitiesinmousebreastcancercelllineGR2H6are10,0.2,and2timesthatofinsulin,respectively,and29%,0.6%,and6%ofthatofIGF-1,indicatingthattheCdomainand9GluofIGF-1areimportantforitsgrowth-promotingactivity.Giventheseresultsandpreviousreports,weproposethattheCdomain,9Glu,and23Phe – 26Asnbetabendareinvolvedinthegrowth-promotingfunctionalregionofIGF-1. IUBMB Life ,49:321 – 325,2000Keywords Growth-promotingfunctionalregion;hybridmolecule;IGF-1;insulin. INTRODUCTION Insulin-likegrowthfactor-1(IGF-1),asamemberofthein-sulinfamily,isasingle-chaingrowthfactorwith70aminoacidresiduescontainingA,B,C,andDdomains( 1 ).TheprimarystructuresoftheAandBdomainsofIGF-1arehighlysimilartotheAandBchainsofinsulin,being52%and45%homol-ogous,respectively.Theirthree-dimensionalstructuresarealsoverysimilar( 2 ).ThebiologicalfunctionsofIGF-1andinsulin Received20January2000;accepted15March2000.