Question

under what condition GTPase-activating protein (GAP) Switches off the RAS-MAPK signaling pathway during EGFR-mediated Ras-activation?

Answer 1

Almost all receptors tyrosine kinases can activate the ras/map K pathway. The Ras protein is monomeric G protein, belongs to the GTPase superfamily of intercellular switch proteins. The activity of the Ras protein is regulated by several factors. Ras activation is accelerated by a guanine nucleotide exchange factor (GEF), which binds to Ras -GDP complex causing dissociation of bound GDP. GTP in cells are high compared to GDP, GTP binds spontaneously with free RAS molecules releasing GEF and formation of RAS-GTP. Deactivation of RAS GTP requires GAP. Activated RAS triggers a kinase cascade in which RAF, MEK and MAP kinases are sequentially phosphorylated and thus activated.

Binding Sos to inactivate Ras causes a large conformational change that permits release of GDP and binding of GTP, forming activate Ras. GAP, which accelerates GTP hydrolysis, is localized near RAS GTP by binding to activated RTK.