Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Ras (H-, K-, N-Ras)

  • Michael S. SamuelEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_67


 H-Ras;  K-Ras;  N-Ras

Historical Background

Evidence that viral genes were translated in virus-transformed cells was first reported in the early 1970s (Green et al. 1971). Following on from these observations, it was discovered that certain 21 kDa proteins encoded by viral genes and possessing guanine nucleotide–binding properties (Scolnick et al. 1979) were essential for the maintenance of transformation in cells infected with the Kirsten and Harvey sarcoma viruses (Shih et al. 1979). Intriguingly, sequences containing a very high degree of homology to genes encoding these transforming proteins were found in normal rat, mouse, and human genomes, suggesting a physiological role, unrelated to disease, for these proteins. Mutant versions of the oncogenes associated with the Kirsten sarcoma virus (K-ras) and the Harvey sarcoma virus (H-ras) were found in cancer cell lines of various tissue origins (Der et al. 1982). The majority of these contained point mutations that resulted...

This is a preview of subscription content, log in to check access.


  1. Brunger AT, Milburn MV, Tong L, deVos AM, Jancarik J, Yamaizumi Z, Nishimura S, Ohtsuka E, Kim SH. Crystal structure of an active form of RAS protein, a complex of a GTP analog and the HRAS p21 catalytic domain. Proc Natl Acad Sci USA. 1990;87:4849–53.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Der CJ, Krontiris TG, Cooper GM. Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses. Proc Natl Acad Sci USA. 1982;79:3637–40.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003;3:11–22.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Elgendy M, Sheridan C, Brumatti G, Martin SJ. Oncogenic Ras-induced expression of Noxa and Beclin-1 promotes autophagic cell death and limits clonogenic survival. Mol Cell. 2011;42:23–35.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Green M, Rokutanda H, Rokutanda M. Virus specific RNA in cells transformed by RNA tumour viruses. Nat New Biol. 1971;230:229–32.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Halaban R, Zhang W, Bacchiocchi A, Cheng E, Parisi F, Ariyan S, Krauthammer M, McCusker JP, Kluger Y, Sznol M. PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells. Pigment Cell Melanoma Res. 2010;23:190–200.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Hall A, Marshall CJ, Spurr NK, Weiss RA. Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1. Nature. 1983;303:396–400.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Hamad NM, Elconin JH, Karnoub AE, Bai W, Rich JN, Abraham RT, Der CJ, Counter CM. Distinct requirements for Ras oncogenesis in human versus mouse cells. Genes Dev. 2002;16:2045–57.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Iyer R, Fetterly G, Lugade A, Thanavala Y. Sorafenib: a clinical and pharmacologic review. Expert Opin Pharmacother. 2010;11:1943–55.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Karnoub AE, Weinberg RA. Ras oncogenes: split personalities. Nat Rev Mol Cell Biol. 2008;9:517–31.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Khosravi-Far R, Solski PA, Clark GJ, Kinch MS, Der CJ. Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation. Mol Cell Biol. 1995;15:6443–53.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Loriot Y, Mordant P, Deutsch E, Olaussen KA, Soria JC. Are RAS mutations predictive markers of resistance to standard chemotherapy? Nat Rev Clin Oncol. 2009;6:528–34.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Potenza N, Vecchione C, Notte A, De Rienzo A, Rosica A, Bauer L, Affuso A, De Felice M, Russo T, Poulet R, et al. Replacement of K-Ras with H-Ras supports normal embryonic development despite inducing cardiovascular pathology in adult mice. EMBO Rep. 2005;6:432–7.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Rodriguez-Viciana P, Warne PH, Khwaja A, Marte BM, Pappin D, Das P, Waterfield MD, Ridley A, Downward J. Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras. Cell. 1997;89:457–67.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Samuel MS, Lourenco FC, Olson MF. K-Ras mediated murine epidermal tumorigenesis is dependent upon and associated with elevated Rac1 activity. PLoS One. 2011;6:e17143.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 2007;7:295–308.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Scolnick EM, Papageorge AG, Shih TY. Guanine nucleotide-binding activity as an assay for src protein of rat-derived murine sarcoma viruses. Proc Natl Acad Sci USA. 1979;76:5355–9.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Sebolt-Leopold JS, Dudley DT, Herrera R, Van Becelaere K, Wiland A, Gowan RC, Tecle H, Barrett SD, Bridges A, Przybranowski S, et al. Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat Med. 1999;5:810–6.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Sefton BM, Trowbridge IS, Cooper JA, Scolnick EM. The transforming proteins of Rous sarcoma virus, Harvey sarcoma virus and Abelson virus contain tightly bound lipid. Cell. 1982;31:465–74.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Shih TY, Weeks MO, Young HA, Scolnick EM. p21 of Kirsten murine sarcoma virus is thermolabile in a viral mutant temperature sensitive for the maintenance of transformation. J Virol. 1979;31:546.PubMedPubMedCentralGoogle Scholar
  21. Smalley KS. PLX-4032, a small-molecule B-Raf inhibitor for the potential treatment of malignant melanoma. Curr Opin Investig Drugs. 2010;11:699–706.PubMedPubMedCentralGoogle Scholar
  22. Sweet RW, Yokoyama S, Kamata T, Feramisco JR, Rosenberg M, Gross M. The product of ras is a GTPase and the T24 oncogenic mutant is deficient in this activity. Nature. 1984;311:273–5.PubMedPubMedCentralCrossRefGoogle Scholar
  23. White E. Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer. 2012;12:401–10.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Centre for Cancer BiologySA Pathology and University of South AustraliaAdelaideAustralia