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Gene Review

Hras  -  Harvey rat sarcoma virus oncogene

Rattus norvegicus

Synonyms: GTPase HRas, H-Ras-1, HRAS1, Hras1, Transforming protein p21, ...
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Disease relevance of Hras


High impact information on Hras

  • Mammalian farnesyltransferase, which attaches a 15 carbon isoprenoid, farnesyl, to a cysteine in p21ras proteins, contains two subunits, alpha and beta [5].
  • We report the identification, purification, and characterization of a farnesyl:protein transferase that transfers the farnesyl moiety from farnesyl pyrophosphate to a cysteine in p21ras proteins [6].
  • Effective peptides included the COOH-terminal sequences of all known p21ras proteins as well as those of lamin A and B [6].
  • Ras (p21ras) interacts directly with the catalytic subunit of phosphatidylinositol-3-OH kinase in a GTP-dependent manner through the Ras effector site [7].
  • A new brain serine/threonine protein kinase may be a target for the p21ras-related proteins Cdc42 and Rac1 [8].

Chemical compound and disease context of Hras


Biological context of Hras


Anatomical context of Hras

  • Expression of Krev-1 and c-H-ras proto-oncogenes in the rat spinal cord and the effects of noxious stimulation [18].
  • Therefore, we investigated the role of pp60c-src and p21ras in rat aortic smooth muscle cell proliferation induced by several G protein-coupled receptors [15].
  • This function is reportedly mediated in part by inhibition of B cell antigen receptor (BCR)-mediated p21ras activation, though the basis of this inhibition is unknown [19].
  • We measured the responses elicited after x irradiation of cells from the normal rat cell line REF52 as well as two oncogene-transformed REF52 cell lines with E1a or E1a plus the mutated c-Harvey-ras T24 (HRAS1 T24) allele [20].
  • We show here that stimulation of the G q protein-coupled angiotensin II (Ang II) receptor causes activation of p21 ras in cardiac myocytes [9].

Associations of Hras with chemical compounds

  • GGA to GAA mutations in the 12th codon of the Hras gene are frequently observed in rat mammary tumors induced by N-nitroso-N-methylurea (NMU) [14].
  • Growth factor receptor binding protein-2 (GRB2) and Shc have been shown to link growth factor receptor activation with guanine nucleotide exchange on p21-ras [21].
  • Various signalling proteins, including nerve growth factor (NGF), p21-ras and src tyrosine kinases, have been suggested to have a role in the regulation of neuronal VDCCs [1].
  • The heterotrimeric G q protein-coupled angiotensin II receptor activates p21 ras via the tyrosine kinase-Shc-Grb2-Sos pathway in cardiac myocytes [9].
  • The first peak of activation of p21ras, at 2-5 min, is mediated by immediate association of phosphorylated Shc with the guanosine exchange factor Sos1 via the adaptor protein Grb2 [22].

Physical interactions of Hras


Regulatory relationships of Hras


Other interactions of Hras


Analytical, diagnostic and therapeutic context of Hras


  1. Regulation of rat neuronal voltage-dependent calcium channels by endogenous p21-ras. Fitzgerald, E.M., Dolphin, A.C. Eur. J. Neurosci. (1997) [Pubmed]
  2. The latent nuclear antigen of Kaposi sarcoma-associated herpesvirus targets the retinoblastoma-E2F pathway and with the oncogene Hras transforms primary rat cells. Radkov, S.A., Kellam, P., Boshoff, C. Nat. Med. (2000) [Pubmed]
  3. Tumorigenic transformation of mammalian cells induced by a normal human gene homologous to the oncogene of Harvey murine sarcoma virus. Chang, E.H., Furth, M.E., Scolnick, E.M., Lowy, D.R. Nature (1982) [Pubmed]
  4. Growth-inhibitory activity and downregulation of the class II tumor-suppressor gene H-rev107 in tumor cell lines and experimental tumors. Sers, C., Emmenegger, U., Husmann, K., Bucher, K., Andres, A.C., Schäfer, R. J. Cell Biol. (1997) [Pubmed]
  5. Protein farnesyltransferase and geranylgeranyltransferase share a common alpha subunit. Seabra, M.C., Reiss, Y., Casey, P.J., Brown, M.S., Goldstein, J.L. Cell (1991) [Pubmed]
  6. Inhibition of purified p21ras farnesyl:protein transferase by Cys-AAX tetrapeptides. Reiss, Y., Goldstein, J.L., Seabra, M.C., Casey, P.J., Brown, M.S. Cell (1990) [Pubmed]
  7. Phosphatidylinositol-3-OH kinase as a direct target of Ras. Rodriguez-Viciana, P., Warne, P.H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M.J., Waterfield, M.D., Downward, J. Nature (1994) [Pubmed]
  8. A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Manser, E., Leung, T., Salihuddin, H., Zhao, Z.S., Lim, L. Nature (1994) [Pubmed]
  9. The heterotrimeric G q protein-coupled angiotensin II receptor activates p21 ras via the tyrosine kinase-Shc-Grb2-Sos pathway in cardiac myocytes. Sadoshima, J., Izumo, S. EMBO J. (1996) [Pubmed]
  10. Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene expression in FRTL-5 cells. II. Down-regulation by v-K-ras oncogene. Perillo, B., Tedesco, I., Laezza, C., Santillo, M., Romano, A., Aloj, S.M., Bifulco, M. J. Biol. Chem. (1995) [Pubmed]
  11. c-H-ras and c-K-ras gene hypomethylation in the livers and hepatomas of rats fed methyl-deficient, amino acid-defined diets. Bhave, M.R., Wilson, M.J., Poirier, L.A. Carcinogenesis (1988) [Pubmed]
  12. Ras involvement in cells transformed with 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) in vitro and with N-[4-(5-nitro-2-furyl)-2-thiazoyl]formamide in vivo. Mann, A.M., Asamoto, M., Chlapowski, F.J., Masui, T., Macatee, T.L., Cohen, S.M. Carcinogenesis (1992) [Pubmed]
  13. Lovastatin prevents angiotensin II-induced cardiac hypertrophy in cultured neonatal rat heart cells. Oi, S., Haneda, T., Osaki, J., Kashiwagi, Y., Nakamura, Y., Kawabe, J., Kikuchi, K. Eur. J. Pharmacol. (1999) [Pubmed]
  14. N-nitroso-N-methylurea-induced rat mammary tumors arise from cells with preexisting oncogenic Hras1 gene mutations. Cha, R.S., Thilly, W.G., Zarbl, H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  15. G protein-coupled receptors control vascular smooth muscle cell proliferation via pp60c-src and p21ras. Schieffer, B., Drexler, H., Ling, B.N., Marrero, M.B. Am. J. Physiol. (1997) [Pubmed]
  16. cAMP antagonizes p21ras-directed activation of extracellular signal-regulated kinase 2 and phosphorylation of mSos nucleotide exchange factor. Burgering, B.M., Pronk, G.J., van Weeren, P.C., Chardin, P., Bos, J.L. EMBO J. (1993) [Pubmed]
  17. Massive programmed cell death in intestinal epithelial cells induced by three-dimensional growth conditions: suppression by mutant c-H-ras oncogene expression. Rak, J., Mitsuhashi, Y., Erdos, V., Huang, S.N., Filmus, J., Kerbel, R.S. J. Cell Biol. (1995) [Pubmed]
  18. Expression of Krev-1 and c-H-ras proto-oncogenes in the rat spinal cord and the effects of noxious stimulation. Murakoshi, T., Hamasaki, H., Ikawa, Y., Urayama, O. Regul. Pept. (1993) [Pubmed]
  19. The RasGAP-binding protein p62dok is a mediator of inhibitory FcgammaRIIB signals in B cells. Tamir, I., Stolpa, J.C., Helgason, C.D., Nakamura, K., Bruhns, P., Daeron, M., Cambier, J.C. Immunity (2000) [Pubmed]
  20. X-ray-induced changes in gene expression in normal and oncogene-transformed rat cell lines. Lambert, M., Borek, C. J. Natl. Cancer Inst. (1988) [Pubmed]
  21. Platelet-derived growth factor stimulates growth factor receptor binding protein-2 association with Shc in vascular smooth muscle cells. Benjamin, C.W., Jones, D.A. J. Biol. Chem. (1994) [Pubmed]
  22. Biphasic activation of p21ras by endothelin-1 sequentially activates the ERK cascade and phosphatidylinositol 3-kinase. Foschi, M., Chari, S., Dunn, M.J., Sorokin, A. EMBO J. (1997) [Pubmed]
  23. The signaling pathway coupling epidermal growth factor receptors to activation of p21ras. Sasaoka, T., Langlois, W.J., Leitner, J.W., Draznin, B., Olefsky, J.M. J. Biol. Chem. (1994) [Pubmed]
  24. Association of MEK1 with p21ras.GMPPNP is dependent on B-Raf. Moodie, S.A., Paris, M.J., Kolch, W., Wolfman, A. Mol. Cell. Biol. (1994) [Pubmed]
  25. Pravastatin, a HMG-CoA reductase inhibitor, blocks the cell cycle progression but not Ca2+ influx induced by IGF-I in FRTL-5 cells. Tada, H., Takada, K., Amino, N., Miyai, K. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  26. Low molecular weight GTP-binding proteins in hepatocytes and an assessment of the role of p21ras proteins in the activation of phospholipase D. Hurst, K.M., Chataway, T.K., Hughes, B.P., Barritt, G.J. Biochem. Int. (1991) [Pubmed]
  27. The mitogen-activated protein kinase cascade is activated by B-Raf in response to nerve growth factor through interaction with p21ras. Jaiswal, R.K., Moodie, S.A., Wolfman, A., Landreth, G.E. Mol. Cell. Biol. (1994) [Pubmed]
  28. cAMP abrogates the p21ras-mitogen-activated protein kinase pathway in fibroblasts. Hordijk, P.L., Verlaan, I., Jalink, K., van Corven, E.J., Moolenaar, W.H. J. Biol. Chem. (1994) [Pubmed]
  29. IL-1 beta transduces different signals than IL-1 alpha leading to class II antigen expression on beta-insulinoma RIN-5AH cells through specific receptors. Vassiliadis, S., Soteriadou, K.P., Papadopoulos, G.K. J. Recept. Signal Transduct. Res. (1997) [Pubmed]
  30. Raf-1 and p21v-ras cooperate in the activation of mitogen-activated protein kinase. Williams, N.G., Paradis, H., Agarwal, S., Charest, D.L., Pelech, S.L., Roberts, T.M. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  31. Identification of a protein associated with p21ras by chemical crosslinking. de Gunzburg, J., Riehl, R., Weinberg, R.A. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  32. Altered expression of mitogen-activated protein kinases in a rat model of experimental hepatocellular carcinoma. McKillop, I.H., Schmidt, C.M., Cahill, P.A., Sitzmann, J.V. Hepatology (1997) [Pubmed]
  33. Oncogenic HRAS suppresses clusterin expression through promoter hypermethylation. Lund, P., Weisshaupt, K., Mikeska, T., Jammas, D., Chen, X., Kuban, R.J., Ungethüm, U., Krapfenbauer, U., Herzel, H.P., Schäfer, R., Walter, J., Sers, C. Oncogene (2006) [Pubmed]
  34. Adenovirus-mediated transfer of a dominant-negative H-ras suppresses neointimal formation in balloon-injured arteries in vivo. Ueno, H., Yamamoto, H., Ito, S., Li, J.J., Takeshita, A. Arterioscler. Thromb. Vasc. Biol. (1997) [Pubmed]
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