Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
The three closely related mammalian ras genes, Hras, Nras and Kras, have each been implicated in human tumorigenesis by virtue of mutational activation. However, while these genes encode proteins with very similar biochemical properties, activating ras alleles corresponding to the various isoforms have been linked to particular malignancies. Accumulating evidence suggests that these proteins exert distinct activities in a tissue-specific context, apparently reflecting developmental lineage-specific roles for the various ras isoforms. Some of these distinct functions appear to reflect differences in their C-termini, which determine distinct subcellular localization, thereby suggesting a role for compartmentalized signaling. In this review, we discuss the biological functions of the ras isoforms in the context of tissue-specific function as it relates to ras function in development and human cancer.