REGULATION OF PROLIFERATION AND APOPTOSIS BY RAS AND RHO GTPASES THROUGH SPECIFIC PHOSPHOLIPID-DEPENDENT SIGNALING

Small GTPases are molecular switches that control signaling pathways c ritical for diverse cellular functions. Recent evidence indicates that multiple effector molecules can be activated by small GTPases. As a r esult, complex biological processes such as cell proliferation and apo ptosis are turned on. Thus, rather than a single linear pathway from t he membrane to the nucleus, the integration of complementary signals i s required for these events to occur, In fact, the coordinated activat ion of small GTPases may constitute some of the critical modulators of those signals triggering either proliferation or cell death. In addit ion to the activation of specific kinases cascades, phospholipid-deriv ed messengers are candidates to compose some of the most critical elem ents associated to regulation of signaling cascades capable of discern ing among life and death. Both proliferation and apoptosis needs compe tence and progression signals. Phospholipase D and sphingomyelinase ma y be important players in this decision-maker step. (C) 1997 Federatio n of European Biochemical Societies.