title: Alternative splicing produces messenger RNAs encoding insulin-like growth factor-I prohormones that are differentially glycosylated in vitro.
abstract: Rat insulin-like growth factor-I (IGF-I) cDNA sequences predict two prohormones that differ in the carboxy-terminal extension peptide (E-peptide) as a result of the inclusion or exclusion of the 52-basepair exon 4 sequence. In the absence of exon 4, the sequence codes for the IGF-Ia prohormone, whose E region contains two potential N-glycosylation sites. With differential splicing and the inclusion of exon 4, the resultant mRNA codes for IGF-Ib, with a longer E-region sequence. In addition, as a consequence of a frame shift, both potential glycosylation sites are lost in the IGF-Ib peptide. We used an in vitro translation system supplemented with canine pancreatic microsomal membranes to analyze cotranslational processing of the IGF-I propeptides. We have demonstrated that IGF-Ia prohormone, which contains two potential N-glycosylation sites in the E region, can be N-glycosylated in vitro, and that both glycosylation sites are probably used. As expected, the IGF-Ib preprohormone is processed by microsomes, but is not glycosylated.
authors.affiliation: Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: M A
authors.initials: MA
authors.lastname: Bach
authors.forename: C T
authors.initials: CT
authors.lastname: Roberts
authors.forename: E P
authors.initials: EP
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: LeRoith
mesh_terms: D000818:Animals; D006031:Glycosylation; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D011817:Rabbits; D051381:Rats; D012156:Reticulocytes / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D011498:Protein Precursors; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I