The insulin family of proteins groups together several evolutionarily related active peptides []: these include insulin [, ], relaxin [, ], insect prothoracicotropic hormone (bombyxin) [], insulin-like growth factors (IGF1 and IGF2) [, ], mammalian Leydig cell-specific insulin-like peptide (gene INSL3), early placenta insulin-like peptide (ELIP) (gene INSL4), locust insulin-related peptide (LIRP), molluscan insulin-related peptides (MIP), and Caenorhabditis elegans insulin-like peptides. The 3D structures of a number of family members have been determined [, , ]. The fold comprises two polypeptide chains (A and B) linked by two disulphide bonds: all share a conserved arrangement of 4 cysteines in their A chain, the first of which is linked by a disulphide bond to the third, while the second and fourth are linked by interchain disulphide bonds to cysteines in the B chain. The IGFs, or somatomedins, play a key role in pre-adolescent mammalian growth. IGF2 appears to be induced by placental lactogen and is thought to play a role in foetal development [].
This entry represents the RNA recognition motif 2 (RRM2) of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).IGF2BP3 plays an important role in the differentiation process during early embryogenesis. It is known to bind to and repress the translation of IGF2 leader 3 mRNA []. IGF2BP3 also acts as a Glioblastoma-specific proproliferative and proinvasive marker acting through IGF2 resulting in the activation of oncogenic phosphatidylinositol 3-kinase/mitogen-activated protein kinase (PI3K/MAPK) pathways []. IGF2BP3 contains four hnRNP K-homology (KH) domains, two RNA recognition motifs (RRMs) and a RGG RNA-binding domain.IGF2BP3 belongs to the IGF2BP family (includes IGF2BP1, IGF2BP2, IGF2BP3). They have different functions, such as cell polarisation, migration, morphology, metabolism, proliferation and differentiation [].
Glypicans [, ]are a group of heparan sulphate proteoglycans which are anchored to cell membranes by a glycosylphosphatidylinositol (GPI) linkage. Structurally, these proteins consist of three separate domains:a) A signal sequence;b) An extracellular domain of about 500 residues that contains 12 conserved cysteines probably involved in disulphide bonds and also contains the sites of attachment of the heparan sulphate glycosaminoglycan side chains;c) A C-terminal hydrophobic region that is post-translationally removed after formation of the GPI-anchor. Six members (GPC1-6) are known in vertebrates []. GPC3 encodes a putative extracellular proteoglycan, glypican 3 that is inferred to play an important role in growth control in embryonic mesodermal tissues in which it is selectively expressed. Initial western- and ligand-blotting experiments suggest that glypican 3 forms a complex with insulin-like growth factor 2 (IGF2), and might thereby modulate IGF2 action []. GPC3 gene defects in a wider range of overgrowth disorders []. GPC3 shares a number of features with the GPC1 [].
The insulin family of proteins groups together several evolutionarily related active peptides []: these include insulin [, ], relaxin [, ], insect prothoracicotropic hormone (bombyxin) [], insulin-like growth factors (IGF1 and IGF2) [, ], mammalian Leydig cell-specific insulin-like peptide (gene INSL3), early placenta insulin-like peptide (ELIP) (gene INSL4), locust insulin-related peptide (LIRP), molluscan insulin-related peptides (MIP) and Caenorhabditis elegans insulin-like peptides. The 3D structures of a number of family members have been determined [, , ]. The fold comprises two polypeptide chains (A and B) linked by two disulphide bonds: all share a conserved arrangement of 4 cysteines in their A chain, the first of which is linked by a disulphide bond to the third, while the second and fourth are linked by interchain disulphide bonds to cysteines in the B chain. The IGFs, or somatomedins, play a key role in pre-adolescent mammalian growth. IGFI expression is regulated by growth hormone and mediates post-natal growth []. Defects in IGF1 are the cause of insulin-like growth factor I deficiency (IGF1 deficiency), an autosomal recessive disorder characterised by growth retardation, sensorineural deafness and mental retardation []. IGF2 appears to be induced by placental lactogen and is thought to play a role in foetal development [].
