PMID:14566968

Citation	McCusker, RH and Novakofski, J (2003) Zinc partitions insulin-like growth factors (IGFs) from soluble IGF binding protein (IGFBP)-5 to the cell surface receptors of BC3H-1 muscle cells. J. Cell. Physiol. 197:388-99
Abstract	Zinc (Zn(2+)) is a multifunctional micronutrient. The list of functions for this micronutrient expanded with the recent discovery that Zn(2+) retains insulin-like growth factors binding proteins (IGFBPs) on the surface of cultured cells, lowers the affinity of cell-associated IGFBPs, and increases the affinity of the cell surface insulin-like growth factor (IGF)-type 1 receptor (IGF-1R). However, currently there is no information concerning the effect of Zn(2+) on soluble IGFBPs. In the current study, the soluble IGFBP-5 secreted by BC(3)H-1 cells is shown to bind approximately 50% more [(125)I]-IGF-II than [(125)I]-IGF-I at pH 7.4. Zn(2+) is shown to depress the binding of both IGF-I and IGF-II to soluble secreted IGFBP-5; [(125)I]-IGF-I binding is affected more so than [(125)I]-IGF-II binding. Zn(2+) acts by lowering the affinity (K(a)) of IGFBP-5 for the IGFs. Scatchard plots are non-linear indicating the presence of high and low affinity binding sites; Zn(2+) affects only binding to the high affinity site. In contrast, Zn(2+) increases the affinity by which either [(125)I]-IGF-I or [(125)I]-R(3)-IGF-I binds to the IGF-1R, but depresses [(125)I]-IGF-II binding to the IGF-type 2 receptor (IGF-2R) on BC(3)H-1 cells. By depressing the association of the IGFs with soluble IGFBPs, Zn(2+) is shown to repartition either [(125)I]-IGF-I or [(125)I]-IGF-II from soluble IGFBP-5 onto cell surface IGF receptors. Zn(2+) was active at physiological doses depressing IGF binding to IGFBP-5 and the IGF-2R at 15-20 microM. Hence, a novel mechanism is further characterized by which the trace micronutrient Zn(2+) could regulate IGF activity.
Links	PubMed Online version:10.1002/jcp.10360
Keywords	Animals; Binding Sites/drug effects; Binding Sites/physiology; Cell Line; Cell Membrane/drug effects; Cell Membrane/metabolism; Extracellular Fluid/drug effects; Extracellular Fluid/metabolism; Insulin-Like Growth Factor Binding Protein 5/drug effects; Insulin-Like Growth Factor Binding Protein 5/metabolism; Macromolecular Substances; Mice; Models, Molecular; Muscle Cells/drug effects; Muscle Cells/metabolism; Protein Binding/drug effects; Protein Binding/physiology; Protein Structure, Tertiary/physiology; Receptor, IGF Type 1/drug effects; Receptor, IGF Type 1/metabolism; Receptor, IGF Type 2/drug effects; Receptor, IGF Type 2/metabolism; Receptors, Cell Surface/drug effects; Receptors, Cell Surface/metabolism; Somatomedins/drug effects; Somatomedins/metabolism; Zinc/metabolism; Zinc/pharmacology
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.