Potential drug targets: small GTPases that regulate leukocyte function

Leukocytes are not only important mediators of innate immunity, but they al so induce and perpetuate inflammatory responses that are harmful to the hos t. Although inflammatory mediators activate leukocytes through a common het erotrimeric G protein (G(i)) signalling intermediate, many downstream infla mmatory functions are regulated by distinct small GTPases, which suggests t hat 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-inflammat ory drugs.