The molecular and cellular biology of insulin-like growth factor II

Abstract

Insulin-like growth factor II (IGF-II) is a 67 amino acid polypeptide that belongs to the family of insulin-like peptides. The IGF-II gene is coupled to the insulin gene and paternally imprinted. Multiple IGF-II mRNAs with identical coding regions and 3′ untranslated regions (UTRs) but different 5′ UTRs are generated from 3 promoters. The transcripts are translationally discriminated and inactivated by a specific endonucleolytic cleavage in their 3′ UTR. These features may be important in the control of IGF-II production. IGF-II functions in an auto- and paracrine manner and binds to two types of receptors. The IGF-I receptor that is a tyrosine kinase and closely related with the insulin receptor and the IGF-II/mannose 6-phosphate ( IGF-II Man 6-P ) receptor that is identical with the cation-independent mannose 6-phosphate receptor. The mitogenic and metabolic actions of IGF-II are propagated by the IGF-I receptor. In contrast, the IGF-II Man 6-P receptor, that target lysosomal enzymes from the Golgi apparatus or the plasma membrane to the lysosomes, mediates the rapid internalization and degradation of IGF-II. IGF-II is expressed at high levels during foetal life and it is a major growth factor for the foetus in rodents. The developmental profiles and tissue distribution of the IGF-I and the maternally imprinted IGF-II Man 6-P receptors both parallel that of IGF-II. In this scenario IGF-II promotes the growth of the embryo through the IGF-I receptor, whereas the IGF-II Man 6-P receptor balance the activity by controlling the extracellular level of IGF-II.