Among the wealth of information that we have gathered about Ras in the past 
decade, the introduction of the concept of space in the field has constituted a 
major revolution that has enabled many pieces of the Ras puzzle to fall into 
place. In the early days, it was believed that Ras functioned exclusively at the 
plasma membrane. Today, we know that within the plasma membrane, the 3 Ras 
isoforms-H-Ras, K-Ras, and N-Ras-occupy different microdomains and that these 
isoforms are also present and active in endomembranes. We have also discovered 
that Ras proteins are not statically associated with these localizations; 
instead, they traffic dynamically between compartments. And we have learned that 
at these localizations, Ras is under site-specific regulatory mechanisms, 
distinctively engaging effector pathways and switching on diverse genetic 
programs to generate different biological responses. All of these processes are 
possible in great part due to the posttranslational modifications whereby Ras 
proteins bind to membranes and to regulatory events such as phosphorylation and 
ubiquitination that Ras is subject to. As such, space and these control 
mechanisms act in conjunction to endow Ras signals with an enormous signal 
variability that makes possible its multiple biological roles. These data have 
established the concept that the Ras signal, instead of being one single, 
homogeneous entity, results from the integration of multiple, site-specified 
subsignals, and Ras has become a paradigm of how space can differentially shape 
signaling.