A novel effector of m-ras and oncogenic, leukomegic member of the ras superfamily

M-Ras is a novel member of the Ras superfamily which is oncogenic and activated by many of the same exchange factors as the classical p21 Ras proteins. However, M-Ras does not bind strongly to classical p21 Ras effectors such as Raf-1, Ral-GDS or PI3 kinases. In order to determine how activated M-Ras exerts its leukemogenic effects and stimulates the differentiation of hemopoietic cells including the generation of platelets, we have used yeast-2-hybrid screens to search for molecules that bind to constitutively active mutants of M-Ras. We have identified a novel protein we termed RPM. RPM is a member of the Ral-GDS family with has a carboxy-terminal Ras-binding domain and a catalytic domain with homology to that of other guanine nucleotide exchange factors. Investigation of the function of RPM using reporter assays indicates that it has strikingly different functions from those reported for other members of the Ral-GDS family. We are interested in the role of RPM and other effectors of M-Ras in regulating the positive and negative effects of M-Ras on the growth of hemopoietic cells, the activation of β1 integrins, and the differentiation of an IL-3-dependent cell line toward the formation of platelets.