The small GTPase Rac suppresses apoptosis caused by serum deprivation in fibroblasts

Background: The small GTPase Rad is a key signaling protein that mediates a number of important physiologic functions including the organization of th e actin cytoskeleton, lipid metabolism, and gene transcription. Rad has als o been implicated in oncogenic transformation. Expression of constitutively active Rac1 in Rat1 fibroblasts elicits serum- and anchorage-independent g rowth and causes tumorigenicity in nude mice. The signaling pathways that m ediate the role of Rac in cell transformation remain to be identified. Here , we study the role of Rac in cell survival in the absence of serum. Materials and Methods: The cell lines used in this study are Rat1 fibroblas ts that express constitutively active or dominant negative mutants of Rac1. We used long-term video time-lapse microscopy to analyze the effects of th ese Rad mutants on mitogenicity and apoptosis. Results: We show that the increase in viability, which is stimulated by Rad in the absence of serum, is predominantly caused by an inhibition of apopt osis, with a minor increase in cell division. We also show that Rad-stimula ted cell viability in serum-starved cells is inhibited by chemical inhibiti on of phosphatidylinositol 3-kinase. Conclusions: Our observations indicate a role for Rac1 in survival signalin g, possibly via activation of phosphatidylinositol 3-kinase. We propose tha t Rac1-stimulated cell survival may contribute to the role off Rac1 in seru m-independent growth and cell transformation.