AN INSULIN-LIKE GROWTH FACTOR-II (IGF-II) ANALOG WITH HIGHLY SELECTIVE AFFINITY FOR IGF-II RECEPTORS STIMULATES DIFFERENTIATION, BUT NOT IGF-I RECEPTOR DOWN-REGULATION IN MUSCLE-CELLS
Sm. Rosenthal et al., AN INSULIN-LIKE GROWTH FACTOR-II (IGF-II) ANALOG WITH HIGHLY SELECTIVE AFFINITY FOR IGF-II RECEPTORS STIMULATES DIFFERENTIATION, BUT NOT IGF-I RECEPTOR DOWN-REGULATION IN MUSCLE-CELLS, Endocrinology, 135(1), 1994, pp. 38-44
The insulin-like growth factors (IGFs) stimulate the growth and differ
entiation of muscle cells. IGF-II, the principal IGF peptide expressed
by differentiating muscle cells, has been implicated in at least two
autocrine/paracrine actions in this tissue: stimulation of differentia
tion and down-regulation of the IGF-I receptor. To determine which IGF
receptor subtypes mediate these effects of IGF-II, we treated mouse B
C3H-1 muscle cells with native IGF-II or [Leu(27)]IGF-II, an analog wi
th high affinity for IGF-II receptors (comparable to that seen with na
tive IGF-II) but markedly seduced affinity for IGF-I and insulin recep
tors. Muscle cell differentiation was assessed by the expression of my
ogenin mRNA and by the binding of alpha-bungarotoxin to the nicotinic
acetylcholine receptor. IGF-I receptor down-regulation was assessed by
receptor binding and mRNA abundance. Although less potent than IGF-II
, the [Leu(27)]IGF-II analog stimulated myogenin gene expression and a
cetylcholine receptor binding in concentrations at which the analog in
teracted with IGF-II receptors, but not significantly with IGF-I recep
tors. In IGF-I receptor down-regulation studies, IGF-II pretreatment s
ignificantly decreased binding of IGF-I to the IGF-I receptor and decr
eased IGF-I receptor mRNA, whereas the IGF-II analog had only minimal
effects. Thus, in addition to the IGF-I receptor which has been previo
usly found to signal IGF-induced myogenesis, these results implicate a
role for the IGF-II receptor in this process. In contrast, IGF-I rece
ptor down-regulation induced by IGF-II is mediated through IGF-I, but
not IGF-II, receptors in muscle cells.