RASGRF1: Proteins and Enzymes

RASGRF1 is 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. Of interest, a region mapping within the amino terminal domain of Ras-GRF1 is similar to both the human breakpoint cluster protein, Bcr, and the Dbl proto-oncogene product, a guanine nucleotide-releasing factor for Cdc42Hs. Ras-GRF2 p135 has also been identified. 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.