The large superfamily of Ras-like GTPases is divided in several families, one of which is the Ras family. In humans this family consists of the three Ras proteins, H-ras, K-ras and N-ras, four Rap proteins, Rap1a, Rap1b, Rap2a, and Rap2b, two R-raslike proteins, R-ras and TC21, two Ral proteins, RalA and RalB, and the recently identified Rheb protein. An important characteristic of this family is Ž. their similarity in the effector domain Fig. 1. This region, also called the switch one region, undergoes a dramatic conformational change during the conversion of the GDP-bound form into the GTP-bound form. In particular, the interaction of the conserved tyrosine 35 with the g-phosphate of GTP is responsible for this alteration. A second region which shows a conformational difference between the GTP-and the GDP-bound form of Ras is the switch two region Ž. aa 60–72. In this region glycine 60 is the conwx served residue that interacts with the g-phosphate 1. A number of proteins bind specifically to the active GTP-bound form of small GTPases and these proteins are putative effector proteins responsible for downstream signalling.