Insulin-ricin B hybrid molecules mediate an insulin-associated effect on cells which do not bind insulin.

Autor: Hofmann, C A, Lotan, R M, Ku, W W, Oeltmann, T N
Zdroj: Journal of Biological Chemistry; October 1983, Vol. 258 Issue: 19 p11774-11779, 6p
Abstrakt: A hybrid molecule was constructed by covalently linking, by a disulfide bridge, the hormone insulin to the binding subunit B of the plant toxin ricin (specificity: Gal, GalNAc). Monolayer-cultured MDCK cells, which lack detectable levels of specific plasma membrane 125I-insulin binding but which readily bind 125I-insulin-ricin B, were used in these studies. Binding of insulin-ricin B to these cells could be displaced by lactose and ricin B, but not by insulin. The biological activity of the hybrid, as measured by [14C]glucose incorporation into glycogen, was stimulated in a dose-dependent manner by the hybrid (10(-11)-10(-8) M), whereas glycogen production was not stimulated by insulin alone. The stimulated glycogen labeling in response to the hybrid was also inhibited by lactose and ricin B. When ricin B alone was tested over the same range of concentrations, stimulation of glycogen synthesis was not observed, nor was there any evidence for stimulation when insulin and ricin B were added simultaneously. These data suggested that alternate cell surface receptors (i.e. ricin B receptors) may substitute for specific receptors (i.e. insulin receptors) to convey intracellular metabolic control signals in this cell line.
Databáze: Supplemental Index