The molecular and cellular biology of insulin-like growth factor II.
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.
Nielsen
F C
FC
Department of Clinical Biochemistry, University Hospital Rigshospitalet, Copenhagen, Denmark.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002468:Cell Physiological Phenomena; D005314:Embryonic and Fetal Development / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017527:Receptor, IGF Type 2 / Q000378:metabolism
D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II