Find Ras Products Interaction Network for Ras Ras Details

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Synonyms: p21 Ras, p21 Ras protein, Ras, Ras protein

Ras Pathway

The mammalian Ras subfamily of small GTPases within the Ras superfamily includes: Ha-Ras; Ki-Ras; N-Ras; M-Ras, R-Ras, RalA, RalB, Pap1A, Rap1B, Rap2A, Rap2B, Tc21, Rit, Rin, Rad, Kir/Gem, Rheb, κβ-Ras1 and κβ-Ras2. Ras-GTPases translocate between the cytosol and the plasma membrane (PM). They are bound in their inactive GDP form in the cytoplasm. They cycle between their inactive GDP and the active GTP bound forms on the plasma membrane. Ras-GTPases are targeted to the PM by post-translational G-protein specific lipid modifications.

Ras-GTPases are activated at the plasma membrane by guanine nucleotide exchange factors (GEF) such as: son of sevenless homologs 1 and 2 (Drosophila) (SOS-1 and SOS-2); Ras protein-specific guanine nucleotide-releasing factor 1 (Cdc25MN/GRF1); Rap guanine nucleotide exchange factor 1 (GRF2); and RasGEF domain family, members 1A, 1B and 1C (RasGRF). They are inactivated by GTPase activating proteins (GAP) such as RAS p21 protein activator (GTPase activating protein) 1 (p120RasGAP) and RAS p21 protein activator 2 (GAP1m). GEF factors are recruited to the plasma membrane by scaffold and adaptor complexes such as SHC/Grb2 that associate with activated tyrosine kinase receptors (TKR). These factors exchange GTP for GDP on the Ras protein. The resulting GTP-Ras protein activates various downstream effectors. A major downstream effector target of Ras-GTP is the MAP-kinase Raf-1 which activates the MEK/ERK gene regulation cascade, a primary cell growth and anti-apoptosis pathway. Ras-GTPases family members regulate the action of other GTPase pathways involving Rap, Ral, Rac and Rho Ras-GTPase. Ras-GTPases also regulate phosphoinositide 3-kinase (PI3K) and phospholipase C (PLC) activities. The direct downstream effectors of Ras activation and cell response depend upon specific members of the Ras subfamily and cell context.