Potential drug targets: small GTPases that regulate leukocyte function

Leukocytes are not only important mediators of innate immunity, but they also induce and perpetuate inflammatory responses that are harmful to the host. Although inflammatory mediators activate leukocytes through a common heterotrimeric G protein (G(i)) signalling intermediate, many downstream inflammatory functions are regulated by distinct small GTPases, which suggests that pharmacological modulation of small GTPase activity would be useful in developing specific anti-inflammatory thera pies. The recent identification of multiple small GTPase effecters, the recognition of the role of GTPase regulatory proteins in directing downstream signalling from small GTPases, and detailed structural information on the GTPases themselves suggests new possibilities for the development of effective and selective anti-inflammatory drugs.