Insulin-like growth factor II: complexity of biosynthesis and receptor binding

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Insulin-like growth factor II (IGF-II) belongs to the insulin family of peptides and acts as a growth factor in many fetal tissues and tumors. The gene expression of IGF-II is initiated at three different promoters which gives rise to multiple transcripts. In a human rhabdomyosarcoma cell line IN 157 IGF-II mRNAs of 6.0-kb, 4.8-kb, and 4.2-kb are present. Fractionation of cellular extracts on sucrose gradients and Northern blot analysis showed that only the 4.8-kb mRNA was associated with polysomes, whereas the other transcripts cosedimented with monosomal particles. This suggests that only the 4.8-kb mRNA is translated to IGF-II. The cell line secretes two forms of immunoreactive and bioactive IGF-II to the medium of molecular size 10 kd and 7.5 kd which may be involved in autocrine control of cell growth. IGF-II binds to two receptors on the surface of many cell types: the IGF-I receptor and the mannose-6-phosphate (Man-6-P)/IGF-II receptor. There is consensus that the cellular effects of IGF-II are mediated by the IGF-I receptor via activation of its intrinsic tyrosine kinase. The Man-6-P/IGF-II receptor is involved in endocytosis of lysosomal enzymes and IGF-II. In selected cell types, however, Man-6-P induces cellular responses. We have studied rat brain neuronal precursor cells where Man-6-P acted as a mitogen suggesting that phosphomannosylated proteins may act as growth factors via the Man-6-P/IGF-II receptor. In conclusion, the gene expression and mechanism of action of IGF-II is very complex suggesting that its biological actions can be regulated at different levels including the transcription, translation, posttranslational processing, receptor binding and intracellular signalling.
Original languageEnglish
Book seriesAdvances in Experimental Medicine and Biology
Pages (from-to)31-44
Number of pages13
Publication statusPublished - 1991

Bibliographical note

Keywords: Animals; Carrier Proteins; Humans; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor II; Mannosephosphates; Protein Biosynthesis; Protein Processing, Post-Translational; Protein-Tyrosine Kinases; RNA, Messenger; Receptor, IGF Type 2; Receptors, Cell Surface

ID: 13885597