The insulin-like growth factor mutation database (IGFmdb)

Abstract

Insulin-like growth factors (IGF-I and IGF-II), and insulin are evolutionarily conserved hormonal regulators of eukaryotic growth and development. Through interactions with their cognate receptors, all three molecules can influence cellular growth, proliferation, differentiation, migration, and survival, as well as metabolic processes. As such, perturbations in signaling by IGFs and insulin are a well-documented cause of altered growth, development and survival during both embryonic and post-natal life. A key approach in understanding how IGFs and insulin elicit their biological effects has been through identifying structural features of the ligands that influence their receptor interactions. Over the years, the study of many hundreds of specifically engineered IGF and insulin analogues has provided a wealth of knowledge about how specific residues of these ligands contribute to ligand:receptor interactions. Some analogues have even provided the basis for designing therapeutic agents for the treatment of IGF and insulin-related diseases. As the list of IGF and insulin analogues continues to grow we find that, while many have been produced and studied, it would be of considerable value to have a central repository from which information about specific analogues and their receptor binding data were readily available in an easily searchable and comparable format. To address this, we have created the "Insulin-like growth factor mutation database" (IGFmdb). The IGFmdb is a web-based curated database of annotated ligand analogues and their receptor binding affinities that can be accessed via http://www.adelaide.edu.au/igfmutation. Currently the IGFmdb contains receptor-binding data for 67 IGF-II analogues that were publicly accessible prior to 2012, as well as 67 IGF-I analogues, including all of those produced and characterised in our laboratory. A small number of these are IGF species homologues. There are also 32 insulin analogues within IGFmdb that were reported within the included IGF analogue studies, representing only a small fraction of existing insulin mutants. Future developments of the IGFmdb will incorporate receptor-binding data for all publicly accessible IGF-I analogues and the data will be expanded to include IGF-binding protein (IGFBP) binding affinities.