The type II insulin-like growth factor (IGF) receptor has low affinity for IGF-I analogs: pleiotypic actions of IGFs on myoblasts are apparently mediated by the type I receptor.
We have characterized binding and several actions of the somatomedins [insulin-like growth factors I and II (IGF-I and IGF-II)] on L6 myoblasts. Both IGF-I and IGF-II are potent stimulators of amino acid uptake, cell proliferation, and differentiation; they also suppress protein degradation in these cells. In all measurements, the relative potencies are IGF-I greater than IGF-II greater than insulin. Two recombinant DNA-produced analogs of IGF-I, (Thr59)IGF-I and (N-Met)IGF-I, were as active as native IGF-I in all four assays. However, when 125I-labeled hormones were used for studies of binding to IGF receptors, there was a striking difference between the native and recombinant IGF-I molecules. Both were bound significantly by the type I receptor (a 350K molecule that is dissociated upon sulfhydryl reduction), but the recombinant analogs exhibited little cross-reactivity with the type II receptor (a 220K molecule that is not dissociated by reduction). Thus, the equal activity of native IGF-I and its recombinant DNA-produced analogs coupled with the higher potency of IGF-I (compared to IGF-II) suggest that the type II receptor plays little or no role in the four actions of the somatomedins studied in L6 myoblasts.
D000345:Affinity Labels; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000502:physiology*; D009132:Muscles / Q000502:physiology*; D011972:Receptor, Insulin / Q000502:physiology*; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins / Q000378:metabolism; D013002:Somatomedins / Q000502:physiology*; D013329:Structure-Activity Relationship
D000345:Affinity Labels; D000596:Amino Acids; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin