Sphingolipids as receptor modulators. An overview.

Abstract

Glycosphingolipids are amphipathic compounds that exist mainly in the plasmalemma with their oligosaccharide portion protruding into the extracellular environment. In this position they are admirably situated for interacting with both ligands and receptors. Binding studies have demonstrated that specific glycolipids function as receptors for some microorganisms and bacterial toxins. Specific oligosaccharides on both glycolipids and glycoproteins bind members of the selection families, and some gangliosides facilitate integrins binding to their ligands. Gangliosides modulate the trophic factor-stimulated dimerization, tyrosine phosphorylation, and subsequent signal transduction events of several tyrosine kinase receptors. GM3 inhibits both the epidermal growth factor receptor and basic fibroblast factor receptor; several gangliosides except GM3 inhibit the platelet-derived growth-factor receptor; GM1 enhances nerve growth-factor-stimulated activation of TrkA; insulin receptor is inhibited to varying degrees by several gangliosides, but 2-->3 sialosylparagloboside is most effective. Activities of the beta(1)-adrenergic and delta-opioid receptors are modulated by GM1. Available information suggests that glycolipids serve as coordinators of multiple receptor functions.