A critical step in signal transduction responses to stimulation of cell surface receptors by their ligands involves the accumulation of Ras proteins in their active GTP-bound state. To reach their active GTP-bound state, Ras proteins must first release bound GDP, a rate limiting step mediated by a guanine nucleotide releasing factor (GRF). The mammalian Ras p21 GRF protein has been designated Ras-GRF1 p140. Ras-GRF1 accelerates release of GDP from H- and N-Ras p21 protein in vitro, but not from the related Ral A or Cdc42Hs GTP-binding proteins.Ras-GRF2 p135 is highly homologous to Ras-GRF1 p140 except in the region between the REM and CDC25 domains and appears to function similarly to Ras-GRF1 p140.