p21 RAS:GTP p21 RAS:GDP SOS mediated nucleotide exchange of RAS (IRS) Authored: Charalambous, M, 2005-01-07 11:17:43 Edited: Schmidt, EE, 0000-00-00 00:00:00 Reactome Database ID Release 43109817 Reactome, http://www.reactome.org ReactomeREACT_1672 SOS promotes the formation of GTP-bound RAS, thus activating this protein. RAS activation results in activation of the protein kinases RAF1, B-Raf, and MAP-ERK kinase kinase (MEKK), and the catalytic subunit of PI3K, as well as of a series of RALGEFs. The activation cycle of RAS GTPases is regulated by their interaction with specific guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). GEFs promote activation by inducing the release of GDP, whereas GAPs inactivate RAS-like proteins by stimulating their intrinsic GTPase activity. NGF-induced RAS activation via SHC-GRB2-SOS is maximal at 2 min but it is no longer detected after 5 min. Therefore, the transient activation of RAS obtained through SHC-GRB2-SOS is insufficient for the prolonged activation of ERKs found in NGF-treated cells.<br>