Actions of insulin-like growth factor-I on the B104 neuronal cell line: effects on cell replication, receptor characteristics, and influence of secreted binding protein on ligand binding.
Several peptide growth factors influence the growth and differentiation of neural cells. To investigate further the growth-promoting effects of the somatomedins on cells of neural origin, the authors characterized the binding and mitogenic effects of insulin-like growth factor-I (IGF-I) on a functionally differentiated rat neuronal cell line (B104). Specific, high-affinity (Kd approximately equal to 10(-9) M) receptors for IGF-I were abundant (approximately 124,000 binding sites/B104 cell). These IGF-I receptors were similar to those of non-neural tissue in that they contained 135,000 dalton binding subunits (demonstrated by affinity labeling and autoradiography) and recognized insulin at high concentrations. IGF-I was more potent than insulin at stimulating B104 cell replication in serum-free medium and, at an initial concentration of 100 ng/ml, was the only exogenous growth factor needed to maintain growth through several cell divisions. Furthermore, cells of later passage were found to secrete specific IGF binding proteins that produced an unusual, biphasic binding curve in radioligand displacement studies. These binding proteins apparently sequester IGF-I, limiting its access to the cell. Experiments with B104 cells may provide useful information about the role of IGFs and their binding proteins as potential regulators of growth and differentiation of the primitive neuroblast.
Orlowski
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CC
Division of Endocrinology, Children's Hospital Medical Center, Elland & Bethesda Avenues, Cincinnati, OH 45229.
Chernausek
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SD
Akeson
R
R
D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D008970:Molecular Weight; D009447:Neuroblastoma; D009474:Neurons; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism*
D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I