RAS GTPase cycle mutants

Stable Identifier
R-HSA-9649913
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
RAS GTPase cycle mutants
Click the image above or here to open this pathway in the Pathway Browser
RAS proteins cycle between an active GTP-bound state and an inactive GDP-bound state. GTPase activating proteins (GAPs) stimulate the low intrinsic GTPase activity of RAS proteins, converting the active to the inactive form, while guanine nucleotide exchange factors (GEFs) stimulate the intrinsic dissociation of GDP, allowing its replacement with GTP and consequent activation of RAS. Disease-causing mutations in RAS promote constitutive signaling by favouring the accumulation of RAS:GTP. The vast majority of these mutations are loss of function mutations at G12, G13 and Q61. These mutations disrupt the GTPase activity of RAS proteins by interfering with nucleophilic attack on the gamma phosphate of GTP. A smaller proportion of RAS mutations increase the intrinsic GDP dissociation rate, while other mutations interfere with RAS interactions with GAPs (reviewed in Prior et al, 2012; Pylayeva-Gupta et al, 2011; Stephen et al, 2014; Samatar and Poulikakos, 2014).
Literature References
PubMed ID Title Journal Year
21993244 RAS oncogenes: weaving a tumorigenic web

Pylayeva-Gupta, Y, Grabocka, E, Bar-Sagi, D

Nat. Rev. Cancer 2011
22589270 A comprehensive survey of Ras mutations in cancer

Prior, IA, Lewis, PD, Mattos, C

Cancer Res. 2012
25435214 Targeting RAS-ERK signalling in cancer: promises and challenges

Samatar, AA, Poulikakos, PI

Nat Rev Drug Discov 2014
24651010 Dragging ras back in the ring

Stephen, AG, Esposito, D, Bagni, RK, McCormick, F

Cancer Cell 2014
Participants
Events
Participates
as an event of
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Cross References
Mondo
Authored
Rothfels, K  (2015-05-18)
Reviewed
Stephens, RM  (2016-08-05)
Created
Rothfels, K  (2019-06-18)
Cite Us!