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Gene Review

Kras  -  v-Ki-ras2 Kirsten rat sarcoma viral...

Mus musculus

Synonyms: AI929937, GTPase KRas, K-Ras 2, K-ras, Ki-Ras, ...
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Disease relevance of Kras


Psychiatry related information on Kras

  • The myc virus induced tumors in diverse organs at a very low frequency and with a long latency period, while approximately 20% of the mice derived from embryos infected with the ras virus developed tumors in the skin with a latency of 4-8 weeks [5].

High impact information on Kras

  • We applied this method to the analysis of a model of Kras2-mediated lung cancer and found a good relationship to human lung adenocarcinoma, thereby validating the model [6].
  • We confirmed the importance of this signature by gene-expression analysis of short hairpin RNA-mediated inhibition of oncogenic Kras2 [6].
  • They enriched, propagated, and differentiated these stem cells in vitro and found that they were activated by the oncogenic protein K-ras [7].
  • This phenotype is associated with an elevated level of ras signaling in Nf1(-/-) endothelial cells and greater nuclear localization of the transcription factor Nfatc1 [8].
  • Rab3a is the most abundant Rab (ras-associated binding) protein in the brain and has a regulatory role in synaptic vesicle trafficking [9].

Chemical compound and disease context of Kras


Biological context of Kras


Anatomical context of Kras

  • This process has been modeled in the mouse by activation of mutant Kras in pancreatic progenitor cells [16].
  • Deregulation of hamster fibroblast proliferation by mutated ras oncogenes is not mediated by constitutive activation of phosphoinositide-specific phospholipase C [17].
  • Three of these tumours, a T-cell lymphoma, a fibrosarcoma and a macrophage tumour, were found to carry an activated c-Ki-ras gene [18].
  • Ki-ras activation was detected in one primary rat liver tumor, and Ha-ras activation was detected in the cell line transformed in vitro with activated aflatoxin B1 [19].
  • These lipid modifications have been suggested to promote or stabilize the association of ras proteins with membranes [20].

Associations of Kras with chemical compounds

  • Neither class of transformants expressing Ki-ras or Ha-ras displayed a significant basal activity of polyphosphoinositide-specific phospholipase C, measured either in serum-starved cells or during exponential growth in the presence of growth factors of the tyrosine kinase family (EGF, FGF, insulin) [17].
  • The encoded protein stimulates the dissociation of guanine nucleotides from the ras-related ralA and ralB GTPases at a rate at least 30-fold faster than the intrinsic nucleotide dissociation rate [21].
  • Farnesol modification of Kirsten-ras exon 4B protein is essential for transformation [20].
  • In addition, inhibition of isoprenoid and cholesterol synthesis with the drug compactin also decreased [Val12]K-ras 4B protein isoprenylation and membrane association [20].
  • The guanosine 5'-(3-O-thio)triphosphate (GTP gamma S)-bound form of smg p21B or the GDP-bound form of smg p21B plus smg GDS also induced DNA synthesis but only in the presence of insulin [22].

Physical interactions of Kras

  • The specificity of this protocol is shown by (a) sensitivity of affinity labeling of ras p21 to known inhibitors of GTP binding and (b) immunoprecipitation of affinity labeled protein with anti-ras p21 serum [23].
  • Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast [24].
  • These ras genes code for a membrane bound protein (ras p21) which has a GTPase activity [25].
  • Codon 12 region of mouse K-ras gene is the site for in vitro binding of transcription factors GATA-6 and NF-Y [26].

Regulatory relationships of Kras


Other interactions of Kras

  • There appears to be selectivity in the activated gene because so far all analyzed tumors induced by carcinogen have activated the N-ras gene, and those induced by radiation have activated the K-ras gene [32].
  • Genetic interaction between Rb and K-ras in the control of differentiation and tumor suppression [33].
  • Taken together, these data suggest that activated Ki-ras may confer genetic instabilty upon cells, possibly through interference with tumor suppressors, such as p53 [34].
  • Differential effects of p21(WAF1/CIP1) deficiency on MMTV-ras and MMTV-myc mammary tumor properties [35].
  • Finally among 18 protooncogenes surveyed, only the accumulation of c-myc and c-K-ras RNAs appears to be associated with the Friend erythroleukemic process before the late leukemic phase develops [13].

Analytical, diagnostic and therapeutic context of Kras

  • Sequence analysis revealed that the most common nucleic acid substitutions were T>A (4/8) in p53, T>C (4/5) in Ikaros and G>A/T (8/9) in Kras, suggesting that the spectrum of mutations was gene dependent [15].
  • To construct mouse tumour models involving K-ras, we used a new gene targeting procedure to create mouse strains carrying oncogenic alleles of K-ras that can be activated only on a spontaneous recombination event in the whole animal [36].
  • Primary transfectant DNAs were analyzed by Southern blot hybridization with DNA probes homologous to c-Ha-ras, c-Ki-ras, and N-ras oncogenes [37].
  • In contrast, upon microinjection of the GTP gamma S-bound form of smg p21B, stress fibers did not markedly decrease and the cells neither became round nor piled up [22].
  • Motivated by cell culture studies suggesting that Ras is a downstream effector of pRb in the control of differentiation, we have examined the tumor and developmental phenotypes of Rb and K-ras double-knockout mice [33].


  1. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Aguirre, A.J., Bardeesy, N., Sinha, M., Lopez, L., Tuveson, D.A., Horner, J., Redston, M.S., DePinho, R.A. Genes Dev. (2003) [Pubmed]
  2. Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder. Braun, B.S., Tuveson, D.A., Kong, N., Le, D.T., Kogan, S.C., Rozmus, J., Le Beau, M.M., Jacks, T.E., Shannon, K.M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  3. Preinvasive pancreatic neoplasia of ductal phenotype induced by acinar cell targeting of mutant Kras in transgenic mice. Grippo, P.J., Nowlin, P.S., Demeure, M.J., Longnecker, D.S., Sandgren, E.P. Cancer Res. (2003) [Pubmed]
  4. Comparison of gene expression and DNA copy number changes in a murine model of lung cancer. Sweet-Cordero, A., Tseng, G.C., You, H., Douglass, M., Huey, B., Albertson, D., Jacks, T. Genes Chromosomes Cancer (2006) [Pubmed]
  5. The ras and myc oncogenes cooperate in tumor induction in many tissues when introduced into midgestation mouse embryos by retroviral vectors. Compere, S.J., Baldacci, P., Sharpe, A.H., Thompson, T., Land, H., Jaenisch, R. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  6. An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis. Sweet-Cordero, A., Mukherjee, S., Subramanian, A., You, H., Roix, J.J., Ladd-Acosta, C., Mesirov, J., Golub, T.R., Jacks, T. Nat. Genet. (2005) [Pubmed]
  7. Stem cells for lung cancer? Berns, A. Cell (2005) [Pubmed]
  8. Nf1 has an essential role in endothelial cells. Gitler, A.D., Zhu, Y., Ismat, F.A., Lu, M.M., Yamauchi, Y., Parada, L.F., Epstein, J.A. Nat. Genet. (2003) [Pubmed]
  9. Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse. Kapfhamer, D., Valladares, O., Sun, Y., Nolan, P.M., Rux, J.J., Arnold, S.E., Veasey, S.C., Bućan, M. Nat. Genet. (2002) [Pubmed]
  10. Genetic alterations of p53 and ras genes in 1,3-butadiene- and 2',3'-dideoxycytidine-induced lymphomas. Zhuang, S.M., Cochran, C., Goodrow, T., Wiseman, R.W., Söderkvist, P. Cancer Res. (1997) [Pubmed]
  11. Mutagenesis of ras proto-oncogenes in rat liver tumors induced by vinyl chloride. Froment, O., Boivin, S., Barbin, A., Bancel, B., Trepo, C., Marion, M.J. Cancer Res. (1994) [Pubmed]
  12. Sulindac sulfone inhibits K-ras-dependent cyclooxygenase-2 expression in human colon cancer cells. Taylor, M.T., Lawson, K.R., Ignatenko, N.A., Marek, S.E., Stringer, D.E., Skovan, B.A., Gerner, E.W. Cancer Res. (2000) [Pubmed]
  13. Protooncogene expression in normal, preleukemic, and leukemic murine erythroid cells and its relationship to differentiation and proliferation. Robert-Lézénès, J., Meneceur, P., Ray, D., Moreau-Gachelin, F. Cancer Res. (1988) [Pubmed]
  14. Cell type-specific tumor suppression by Ink4a and Arf in Kras-induced mouse gliomagenesis. Uhrbom, L., Kastemar, M., Johansson, F.K., Westermark, B., Holland, E.C. Cancer Res. (2005) [Pubmed]
  15. Frequent retention of heterozygosity for point mutations in p53 and Ikaros in N-ethyl-N-nitrosourea-induced mouse thymic lymphomas. Kakinuma, S., Nishimura, M., Kubo, A., Nagai, J.Y., Amasaki, Y., Majima, H.J., Sado, T., Shimada, Y. Mutat. Res. (2005) [Pubmed]
  16. Chromosomal instability in mouse metastatic pancreatic cancer--it's Kras and Tp53 after all. Siveke, J.T., Schmid, R.M. Cancer Cell (2005) [Pubmed]
  17. Deregulation of hamster fibroblast proliferation by mutated ras oncogenes is not mediated by constitutive activation of phosphoinositide-specific phospholipase C. Seuwen, K., Lagarde, A., Pouysségur, J. EMBO J. (1988) [Pubmed]
  18. Three different activated ras genes in mouse tumours; evidence for oncogene activation during progression of a mouse lymphoma. Vousden, K.H., Marshall, C.J. EMBO J. (1984) [Pubmed]
  19. Activation of ras oncogene in aflatoxin-induced rat liver carcinogenesis. Sinha, S., Webber, C., Marshall, C.J., Knowles, M.A., Proctor, A., Barrass, N.C., Neal, G.E. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  20. Farnesol modification of Kirsten-ras exon 4B protein is essential for transformation. Jackson, J.H., Cochrane, C.G., Bourne, J.R., Solski, P.A., Buss, J.E., Der, C.J. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  21. Characterization of a guanine nucleotide dissociation stimulator for a ras-related GTPase. Albright, C.F., Giddings, B.W., Liu, J., Vito, M., Weinberg, R.A. EMBO J. (1993) [Pubmed]
  22. Microinjection of smg/rap1/Krev-1 p21 into Swiss 3T3 cells induces DNA synthesis and morphological changes. Yoshida, Y., Kawata, M., Miura, Y., Musha, T., Sasaki, T., Kikuchi, A., Takai, Y. Mol. Cell. Biol. (1992) [Pubmed]
  23. An affinity labeling of ras p21 protein and its use in the identification of ras p21 in cellular and tissue extracts. Basu, A., Modak, M.J. J. Biol. Chem. (1987) [Pubmed]
  24. Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast. Qian, Y.W., Lee, E.Y. J. Biol. Chem. (1995) [Pubmed]
  25. Mechanism of carcinogenesis: the role of oncogenes, transcriptional enhancers and growth factors. Spandidos, D.A. Anticancer Res. (1985) [Pubmed]
  26. Codon 12 region of mouse K-ras gene is the site for in vitro binding of transcription factors GATA-6 and NF-Y. Gorshkova, E.V., Kaledin, V.I., Kobzev, V.F., Merkulova, T.I. Biochemistry Mosc. (2005) [Pubmed]
  27. K-ras regulates the steady-state expression of matrix metalloproteinase 2 in fibroblasts. Liao, J., Wolfman, J.C., Wolfman, A. J. Biol. Chem. (2003) [Pubmed]
  28. Radiation and chemical activation of ras oncogenes in different mouse strains. Newcomb, E.W., Diamond, L.E., Sloan, S.R., Corominas, M., Guerrerro, I., Pellicer, A. Environ. Health Perspect. (1989) [Pubmed]
  29. Mist1-KrasG12D knock-in mice develop mixed differentiation metastatic exocrine pancreatic carcinoma and hepatocellular carcinoma. Tuveson, D.A., Zhu, L., Gopinathan, A., Willis, N.A., Kachatrian, L., Grochow, R., Pin, C.L., Mitin, N.Y., Taparowsky, E.J., Gimotty, P.A., Hruban, R.H., Jacks, T., Konieczny, S.F. Cancer Res. (2006) [Pubmed]
  30. Transforming and c-fos promoter/enhancer-stimulating activities of a stimulatory GDP/GTP exchange protein for small GTP-binding proteins. Fujioka, H., Kaibuchi, K., Kishi, K., Yamamoto, T., Kawamura, M., Sakoda, T., Mizuno, T., Takai, Y. J. Biol. Chem. (1992) [Pubmed]
  31. Radiosensitizing Effects of the Prenyltransferase Inhibitor AZD3409 against RAS Mutated Cell Lines. Cengel, K.A., Deutsch, E., Stephens, T.C., Voong, K.R., Kao, G.D., Bernhard, E.J. Cancer Biol. Ther. (2006) [Pubmed]
  32. A molecular approach to leukemogenesis: mouse lymphomas contain an activated c-ras oncogene. Guerrero, I., Calzada, P., Mayer, A., Pellicer, A. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  33. Genetic interaction between Rb and K-ras in the control of differentiation and tumor suppression. Takahashi, C., Contreras, B., Bronson, R.T., Loda, M., Ewen, M.E. Mol. Cell. Biol. (2004) [Pubmed]
  34. Correlation of genetic instability and apoptosis in the presence of oncogenic Ki-Ras. Chen, C.Y., Liou, J., Forman, L.W., Faller, D.V. Cell Death Differ. (1998) [Pubmed]
  35. Differential effects of p21(WAF1/CIP1) deficiency on MMTV-ras and MMTV-myc mammary tumor properties. Bearss, D.J., Lee, R.J., Troyer, D.A., Pestell, R.G., Windle, J.J. Cancer Res. (2002) [Pubmed]
  36. Somatic activation of the K-ras oncogene causes early onset lung cancer in mice. Johnson, L., Mercer, K., Greenbaum, D., Bronson, R.T., Crowley, D., Tuveson, D.A., Jacks, T. Nature (2001) [Pubmed]
  37. Identification of an activated c-Ki-ras oncogene in rat liver tumors induced by aflatoxin B1. McMahon, G., Hanson, L., Lee, J.J., Wogan, G.N. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
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