Mechanisms of receptor-mediated transmembrane signalling

Although this paper has dealt with general mechanisms whereby a hormonal signal is transmitted across the cell membrane, advances in work with a number of receptors should permit a precision of description of these mechanisms that would have delighted both Langley and Ehrlich. For instance, the detailed sequences now known for the separate subunits of the nicotinic cholinergic receptor and the cellular manipulations made possible by the cloning of the separate subunit genes will make it possible to determine the precise receptor sequence involved either in acetylcholine binding or in ion channel function. The complete sequences and biochemical properties now known for the insulin and EGF-URO receptors to be dealt with in part by a subsequent article (van Obberghen and Gammeltoft, this series) should lay the groundwork for elucidating the transmembrane signalling mechanisms used by the kinase family of growth factor receptors. Continuing work on the structure of the beta-adrenergic receptor, and on the interaction of such receptors with guanine nucleotide regulatory complexes and on the detailed properties of the family of so-called G-proteins and their associated regulatory subunits should unravel the details for a variety of transmembrane signalling reactions. Thus, at least for three basic transmembrane signalling mechanisms: ligand modulated ion transport; ligand-modulated receptor enzyme activity (e.g. tyrosine kinase); and ligand-modulated liberation of cryptic mediators (like the alpha- and beta-subunits of the guanine nucleotide regulatory complexes) one can look forward with excitement to the elucidation in the not-too-distant future of a number of specific biochemical reaction pathways that lead to cell activation.