Signaling by RAS mutants

Stable Identifier
Homo sapiens
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Members of the RAS gene family were the first oncogenes to be identified, and mutations in RAS are present in ~20-30% of human cancers (reviewed in Prior et al, 2012). Mutations in the KRAS gene are the most prevalent, and are found with high frequency in colorectal cancer, non-small cell lung cancer and pancreatic cancer, among others. The reasons for the lower prevalence of HRAS and NRAS mutations in human cancers are not fully understood, but may reflect gene-specific functions as well as differential codon usage and spatio-temporal regulation (reviewed in Prior et al, 2012; Stephen et al, 2014; Pylayeva-Gupta et al, 2011). Activating RAS mutations contribute to cellular proliferation, transformation and survival by activating the MAPK signaling pathway, the AKT pathway and the RAL GDS pathway, among others (reviewed in Stephen et al, 2014; Pylayeva-Gupta et al, 2011).

Although the frequency and distribution varies between RAS genes and cancer types, the vast majority of activating RAS mutations occur at one of three residues - G12, G13 and Q61. Mutations at these sites favour the RAS:GTP bound form and yield constitutively active versions of the protein (reviewed in Prior et al, 2012).

Literature References
PubMed ID Title Journal Year
21993244 RAS oncogenes: weaving a tumorigenic web

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

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

Lewis, PD, Mattos, C, Prior, IA

Cancer Res. 2012
24651010 Dragging ras back in the ring

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

Cancer Cell 2014
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Noonan syndrome DOID:3490 Turner's phenotype, karyotype normal (disorder)
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