Why cytoplasmic signalling proteins should be recruited to cell membranes

It has been suggested that localization of signal-transduction proteins clo se to the cell membrane causes an increase in their rate of encounter after activation. We maintain that such an increase in the first-encounter rate is too small to be responsible for truly enhanced signal transduction. Inst ead, the function of membrane localization is to increase the number (or av erage lifetime) of complexes between cognate signal transduction proteins a nd hence increase the extent of activation of downstream processes. This is achieved by concentrating the proteins in the small volume of the area jus t below the plasma membrane. The signal-transduction chain is viewed simply as operating at low default intensity because one of its components is pre sent at a low concentration. The steady signalling level of the chain is en hanced 1000-fold by increasing the concentration of that component. This oc curs upon 'piggyback' binding to a membrane protein, such as the activated receptor, initiating the signal-transduction chain. For the effect to occur , the protein translocated to the membrane cannot be free but has to remain organized by being piggyback bound to a receptor, membrane lipid(s) or sca ffold. We discuss an important structural constraint imposed by this mechan ism on signal transduction proteins that might also account for the presenc e of adaptor proteins.