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Cells are constantly exposed to a multitudeof environmental cues. In order to respondappropriately to a given stimulus, integratedanalysis of the provided information isrequired. To this end, signal transductionpathways, the cellular communicationhighways responsible for linking externalcues via receptors to changes in cell cytosoland nucleus, must be cross-linked in anetwork. In the jargon of signaltransduction, this process is referred to as“cross-talk” between signaling pathways.Inherent to this process is the ability ofindividual elements to interact not onlywith components of the same pathway butalso those from different ones. At themolecular level, the importance of thisaspect to signaling is perhaps bestunderscored by the existence of so-calledscaffolding proteins, which, in the absenceof enzymatic activity, function by linkingmultiple proteins from the same or differentpathways. Hence, alterations in cellularbehavior may be viewed as the consequenceof a multitude of protein-protein, protein-lipid and protein-DNA interactionsassociated with signaling.Today, the secrets of signal transductionare being unraveled at a steadily increasingpace thanks to the availability of genomesequences from various species, includinghumans. Perhaps, one important insightfrom the analysis of such data is thatproteins are modular by nature. Althoughthe existence of specific protein moduleswas well accepted prior to the advent ofgenome sequencing, the sheer magnitudenow apparent was unexpected.Furthermore, given that genome size clearlydoes not reflect the functional complexityof an organism, some speculate that thischaracteristic may be more faithfullyencrypted in modularity of the resultingproteins (Lawler, 2003).Some years ago, the question was raisedas to why proteins are so large (Srere,1984). This enigma has now been solvedrather elegantly: protein domainsresponsible for enzymatic activity arecombined with modules responsible forcorrect spatial and temporal regulation ofprotein localization. Furthermore,functional analysis has revealed that thesetraits –activity and positional information–are crucial for correct protein function.Most intriguingly, many experiments cannow be designed more rationally thanks toguidance provided by computerizedanalysis of the wealth of informationavailable in different sequence databases.Currently, enormous resources are beinginvested in an attempt to combine genetics,molecular and cellular biology, medicine aswell as biochemistry to understand not only

Supramolecular complex formation in cell signaling and disease: an update on a recurrent theme in cell life and death