Evolution of insulin-like growth factor-I (IGF-I) action: in vitro characterization of vertebrate IGF-I proteins.
While there is considerable structural evidence that IGFs share a long evolutionary history, less is known about the conservation of IGF action. These studies have primarily been hampered by the small amounts of purified IGFs that have been available for testing. More recently, however, we have adopted recombinant strategies to produce milligram quantities of IGFs for biological studies. Thus we have been able to compare the properties of rat, kangaroo, chicken, salmon and barramundi IGF-I, proteins that differ from human IGF-I by 3, 6, 8, 14 and 16 amino acids respectively. While we have found that the IGF-I proteins exhibit similar biological activities and type-I IGF receptor binding affinities, regardless of whether mammalian, avian or piscine cell lines are used, there was a trend suggesting that the fish proteins at least, were most effective in studies using homologous systems. Thus, salmon IGF-I was not as potent as human IGF-I in bioassays in mammalian cells, but was as effective as human IGF-I in piscine cells. As expected, the IGF-I proteins competed poorly for binding to type-2 receptors present on ovine placental membranes. Interestingly however, the two fish IGF-I proteins exhibited greater affinity for this receptor than the other IGF-I proteins, hence reminiscent of the results previously found with recombinant hagfish IGF. Despite these small differences, these results taken together indicate that the IGF-I proteins appear to have been remarkably conserved in both structure and in vitro action during vertebrate radiation.
Upton
Z
Z
Cooperative Research Centre for Tissue Growth and Repair, School of Biology, Flinders University of South Australia, Adelaide, Australia. zee.upton@flinders.edu.au
Yandell
C A
CA
Degger
B G
BG
Chan
S J
SJ
Moriyama
S
S
Francis
G L
GL
Ballard
F J
FJ
D000595:Amino Acid Sequence; D000818:Animals; D002642:Chick Embryo; D019143:Evolution, Molecular; D005399:Fishes; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology*; D008969:Molecular Sequence Data; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity