DISTRIBUTION AND BINDING-PROPERTIES OF RECEPTORS FOR LEUKEMIA INHIBITORY FACTOR
- Author(s)
- Hilton, DJ; Nicola, NA; Metcalf, D;
- Journal Title
- CIBA FOUNDATION SYMPOSIA
- Publication Type
- Journal Article
- Abstract
- The pleiotropic biological actions of leukaemia inhibitory factor (LIF) on haemopoietic cells (macrophages and megakaryocytes), hepatocytes, osteoblasts, pre-adipocytes, embryonic stem cells, myoblasts and neuronal cells must be mediated through the interactions of LIF with specific cellular receptors. The demonstration by equilibrium binding analysis and autoradiography of LIF receptors on all of the above cells and cell lines suggests that each of these pleiotropic effects of LIF is mediated by direct interactions with the responding cells rather than by the indirect release of secondary cytokines. Despite the differing biological effects of LIF on these cells, equilbrium binding, kinetic analyses and receptor internalization studies have all suggested that these cells display essentially identical high affinity LIF receptors. Nevertheless, there is evidence on some cell types (granulocyte-macrophage colony-stimulating factor [GM-CSF] transgenic peritoneal cells and F9 embryonal carcinoma cells) for a second class of low affinity LIF receptors (K(d) = 1.5 nM versus K(d) = 30 pM for high affinity receptors) which differ from the high affinity receptors only in kinetic dissociation rate. Moreover, the evidence suggests that low and high affinity receptors are structurally related and interconvertible, because detergent solubilization of LIF receptors from any cell type results in the quantitative conversion of high affinity receptors into low affinity receptors. As is the case for other related cytokine receptors, these data suggest that high affinity LIF receptors may be composed of two protein subunits-one responsible for LIF-specific low affinity binding and the other responsible for affinity conversion and cell signalling by the receptor. Such a model provides a possible explanation for the pleiotropy of LIF's biological actions.
- Publisher
- JOHN WILEY & SONS LTD
- Keywords
- STIMULATING FACTOR; CELLS; PURIFICATION; DIFFERENTIATION
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1992-01-01 12:00:00