COMPETITION BY 2ND-MESSENGER SYSTEMS FOR RECEPTOR INTERACTION AND ACTIVATION - IMPLICATIONS FOR TISSUE-SPECIFIC RESPONSES AND DISEASE THERAPY

1. At any one instant, most receptors are now recognized to be able to stimulate multiple signal transduction pathways in a cell when activa ted by an appropriate hormone. These different signalling pathways app ear to allow for distinct cellular responses, such as cell proliferati on, differentiation, and shape change, 2. In addition, many different types of cell will possess the same type of receptor Therefore, for a hormone to be able to transmit differential signals to the various cel l types able to respond to it, cells must discriminate the stimulus at some point, Such discrimination would seem to be an absolute requirem ent to allow a tissue-specific response to an identical initial stimul us, In theory, this specificity could occur at many points in the rece ptor signal transduction cascade, including cytosolic receptor couplin g systems and tissue/cell-specific responsive genes, 3. The present pa per summarizes our work and that of others which has determined some o f the coupling systems of G-protein-coupled receptors and tyrosine kin ase receptors and how these systems may be interacting, 4. In addition to these theoretical considerations, a potential therapeutic strategy underlies the ability of receptors to couple to more than one signal transduction system, If a response to a hormone were, for example, eit her cell proliferation or cell morphological change or differentiation and separate receptor-coupled signalling systems were responsible for these effects, pharmacological intervention may allow the transfer fr om one signalling system to another, If such a change allowed a perman ent change to the differentiated phenotype, this could potentially for m the basis of a signal-based cancer therapy.