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Gene Review

ROS1  -  ROS proto-oncogene 1 , receptor tyrosine...

Homo sapiens

Synonyms: MCF3, Proto-oncogene c-Ros, Proto-oncogene c-Ros-1, Proto-oncogene tyrosine-protein kinase ROS, ROS, ...
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Disease relevance of ROS1


Psychiatry related information on ROS1


High impact information on ROS1

  • We have perfused the inside-out preparation of a frog rod outer segment (I/O ROS, originally termed truncated ROS, and find that Ca2+ in a physiological range regulates the light-activation of PDE [9].
  • High specific activity estradiol labeled with iodine-125 was used to detect approximately 200 saturable, high-affinity (dissociation constant approximately equal to 1.0 nM) nuclear binding sites in rat (ROS 17/2.8) and human (HOS TE85) clonal osteoblast-like osteosarcoma cells [10].
  • Thus, our findings add SUMO conjugating enzymes to the small list of specific direct effectors of H(2)O(2) and implicate ROS as key regulators of the sumoylation-desumoylation equilibrium [11].
  • The same phenomenon is also observed in a physiological scenario of endogenous ROS production, the respiratory burst in macrophages [11].
  • Proinflammatory cytokines such as GM-CSF and TNF-alpha prime ROS production by neutrophils through unknown mechanisms [12].

Chemical compound and disease context of ROS1


Biological context of ROS1

  • The fused protein product FIG-ROS is a potent oncogene, and its transforming potential resides in its ability to interact with and become localized to the Golgi apparatus [18].
  • Both v-ros and mcf3 can encode a protein with homology to tyrosine-specific protein kinases, and both mcf3 and v-ros encode a potential transmembrane domain N terminal to the kinase domain. mcf3 probably arose during gene transfer from a normal human ros gene by the loss of a putative extracellular domain [19].
  • The transmembrane proto-oncogene receptor tyrosine kinase (RTK) ROS is an orphan receptor that is aberrantly expressed in neoplasms of the central nervous system [13].
  • The FIG-ROS transcript is encoded by 7 FIG exons and 9 ROS-derived exons [13].
  • Both MC3T3 and EROS cells showed increased cell growth in response to EGF, whereas ROS cells did not [20].

Anatomical context of ROS1

  • The ROS1 gene was present in normal copy numbers in all cell lines that expressed the gene [1].
  • The human ROS1 gene, which possibly encodes a growth factor receptor, was found to be expressed in human tumor cell lines [1].
  • In conclusion, collectively our findings demonstrate that unconjugated bile acids activate hepatocyte receptor tyrosine kinases and intracellular signaling pathways in a ROS-dependent manner [21].
  • UV radiation down-regulates Dsg-2 via Rac/NADPH oxidase-mediated generation of ROS in human lens epithelial cells [22].
  • In this work the influence of H_{2}O_{2} on the ability of human blood monocytes to generate ROS upon stimulation of cells by adhesion to glass surface and fMLP was studied using the luminol-dependent chemiluminescence (LDCL) method [23].

Associations of ROS1 with chemical compounds

  • No comparable similarities in the extracellular domains were found between ROS1 and other receptor-type tyrosine kinases [24].
  • Bile acid-induced AKT activation was blunted by preventing ERBB1 activation and ROS generation [21].
  • The AT-I appeared to exhibit both pro-oxidant and antioxidant properties after an ESR spectrometer was used to detect hydroxyl radical productions in vitro and flow cytometry to detect intracellular ROS productions in AT-I treated cells [25].
  • The potential role of melatonin as an antioxidant by scavenging and detoxifying ROS raised the possibility that compounds that are analogous to melatonin can also be used for their antioxidant properties [26].
  • Most glioblastoma-derived cell lines express an 8.3 kb ros1 transcript and a 280 kD glycoprotein designated gp280ros1, which can be specifically immunoprecipitated with an anti-ROS antibody [27].

Regulatory relationships of ROS1

  • This data also argues that GST- MDA-7 induces two parallel pro-apoptotic pathways via ROS-dependent and -independent mechanisms [28].
  • Catalase addition prevented H(2)O(2)-induced ROS production, ERKs protein phosphorylation, and cell death, and BE dose-dependently inhibited H(2)O(2)-induced ERK protein phosphorylation in C6 cells [29].

Other interactions of ROS1

  • A microdeletion on 6q21 results in the fusion of FIG, a gene coding for a Golgi apparatus-associated protein, to the kinase domain of the protooncogene c-ROS [18].
  • The role of HO-1 in ROS-scavenging activity of BE is proposed [29].
  • One of the malignant meningioma included in the study was clearly negative for bcl2 as well as ROS1 [30].
  • The Thiazolidinedions (TZDs) are Insulin Sensitizers (e.g Rosiglitazone = ROS, Pioglitazone = PIO) introduced into clinical practice in 1997; clinical evidence data showed that TZDs improved both HOMA-R, and HOMA-B [31].
  • Both NGF and CNTF were capable of preventing ROS mediated neuronal death following in vitro JEV infection to a certain extent [32].

Analytical, diagnostic and therapeutic context of ROS1


  1. Expression and rearrangement of the ROS1 gene in human glioblastoma cells. Birchmeier, C., Sharma, S., Wigler, M. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  2. Human c-ros-1 gene homologous to the v-ros sequence of UR2 sarcoma virus encodes for a transmembrane receptorlike molecule. Matsushime, H., Wang, L.H., Shibuya, M. Mol. Cell. Biol. (1986) [Pubmed]
  3. TNFalpha induces chromosomal abnormalities independent of ROS through IKK, JNK, p38 and caspase pathways. Higashimoto, T., Panopoulos, A., Hsieh, C.L., Zandi, E. Cytokine (2006) [Pubmed]
  4. CAGE, a novel cancer/testis antigen gene, promotes cell motility by activation ERK and p38 MAPK and downregulating ROS. Shim, H., Shim, E., Lee, H., Hahn, J., Kang, D., Lee, Y.S., Jeoung, D. Mol. Cells (2006) [Pubmed]
  5. Expression of the ROS1 oncogene for tyrosine receptor kinase in adult human meningiomas. Zhao, J.F., Sharma, S. Cancer Genet. Cytogenet. (1995) [Pubmed]
  6. The role of reactive oxygen and nitrogen species in airway epithelial gene expression. Martin, L.D., Krunkosky, T.M., Voynow, J.A., Adler, K.B. Environ. Health Perspect. (1998) [Pubmed]
  7. Methamphetamine-induced dopaminergic neurotoxicity: role of peroxynitrite and neuroprotective role of antioxidants and peroxynitrite decomposition catalysts. Imam, S.Z., el-Yazal, J., Newport, G.D., Itzhak, Y., Cadet, J.L., Slikker, W., Ali, S.F. Ann. N. Y. Acad. Sci. (2001) [Pubmed]
  8. Myoinositol/folic acid combination for the treatment of erectile dysfunction in type 2 diabetes men: a double-blind, randomized, placebo-controlled study. Agostini, R., Rossi, F., Pajalich, R. European review for medical and pharmacological sciences (2006) [Pubmed]
  9. Calcium-dependent regulation of cyclic GMP phosphodiesterase by a protein from frog retinal rods. Kawamura, S., Murakami, M. Nature (1991) [Pubmed]
  10. Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells. Komm, B.S., Terpening, C.M., Benz, D.J., Graeme, K.A., Gallegos, A., Korc, M., Greene, G.L., O'Malley, B.W., Haussler, M.R. Science (1988) [Pubmed]
  11. Regulation of SUMOylation by reversible oxidation of SUMO conjugating enzymes. Bossis, G., Melchior, F. Mol. Cell (2006) [Pubmed]
  12. A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites. Dang, P.M., Stensballe, A., Boussetta, T., Raad, H., Dewas, C., Kroviarski, Y., Hayem, G., Jensen, O.N., Gougerot-Pocidalo, M.A., El-Benna, J. J. Clin. Invest. (2006) [Pubmed]
  13. Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21). Charest, A., Lane, K., McMahon, K., Park, J., Preisinger, E., Conroy, H., Housman, D. Genes Chromosomes Cancer (2003) [Pubmed]
  14. Increased stability of P21(WAF1/CIP1) mRNA is required for ROS/ERK-dependent pancreatic adenocarcinoma cell growth inhibition by pyrrolidine dithiocarbamate. Donadelli, M., Dalla Pozza, E., Costanzo, C., Scupoli, M.T., Piacentini, P., Scarpa, A., Palmieri, M. Biochim. Biophys. Acta (2006) [Pubmed]
  15. Association between the expression of the c-myc oncogene mRNA and the expression of the receptor protein for 1,25-dihydroxyvitamin D3. Manolagas, S.C., Provvedini, D.M., Murray, E.J., Murray, S.S., Tsonis, P.A., Spandidos, D.A. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  16. The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status. Pérez-Galán, P., Roué, G., Villamor, N., Montserrat, E., Campo, E., Colomer, D. Blood (2006) [Pubmed]
  17. 1,25-Dihydroxycholecalciferol and glucocorticosteroid regulation of adenylate cyclase in an osteoblast-like cell line. Catherwood, B.D. J. Biol. Chem. (1985) [Pubmed]
  18. Oncogenic targeting of an activated tyrosine kinase to the Golgi apparatus in a glioblastoma. Charest, A., Kheifets, V., Park, J., Lane, K., McMahon, K., Nutt, C.L., Housman, D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  19. Characterization of an activated human ros gene. Birchmeier, C., Birnbaum, D., Waitches, G., Fasano, O., Wigler, M. Mol. Cell. Biol. (1986) [Pubmed]
  20. Down-regulation of osteoblastic cell differentiation by epidermal growth factor receptor. Chien, H.H., Lin, W.L., Cho, M.I. Calcif. Tissue Int. (2000) [Pubmed]
  21. Conjugated bile acids promote ERK1/2 and AKT activation via a pertussis toxin-sensitive mechanism in murine and human hepatocytes. Dent, P., Fang, Y., Gupta, S., Studer, E., Mitchell, C., Spiegel, S., Hylemon, P.B. Hepatology (2005) [Pubmed]
  22. UV radiation down-regulates Dsg-2 via Rac/NADPH oxidase-mediated generation of ROS in human lens epithelial cells. Jiang, Q., Zhou, C., Healey, S., Chu, W., Kouttab, N., Bi, Z., Wan, Y. Int. J. Mol. Med. (2006) [Pubmed]
  23. Activation of redox-systems of monocytes by hydrogen peroxide. Krjukov, A.A., Semenkova, G.N., Cherenkevich, S.N., Gerein, V. Biofactors (2006) [Pubmed]
  24. Characterization of ROS1 cDNA from a human glioblastoma cell line. Birchmeier, C., O'Neill, K., Riggs, M., Wigler, M. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  25. Pro-oxidant and cytotoxic activities of atractylenolide I in human promyeloleukemic HL-60 cells. Wang, C.C., Lin, S.Y., Cheng, H.C., Hou, W.C. Food Chem. Toxicol. (2006) [Pubmed]
  26. Synthesis and evaluation of in vitro antioxidant capacities of some benzimidazole derivatives. Gurer-Orhan, H., Orhan, H., Suzen, S., Püsküllü, M.O., Buyukbingol, E. Journal of enzyme inhibition and medicinal chemistry. (2006) [Pubmed]
  27. Characterization of the ros1-gene products expressed in human glioblastoma cell lines. Sharma, S., Birchmeier, C., Nikawa, J., O'Neill, K., Rodgers, L., Wigler, M. Oncogene Res. (1989) [Pubmed]
  28. MDA-7 regulates cell growth and radiosensitivity in vitro of primary (non-established) human glioma cells. Yacoub, A., Mitchell, C., Hong, Y., Gopalkrishnan, R.V., Su, Z.Z., Gupta, P., Sauane, M., Lebedeva, I.V., Curiel, D.T., Mahasreshti, P.J., Rosenfeld, M.R., Broaddus, W.C., James, C.D., Grant, S., Fisher, P.B., Dent, P. Cancer Biol. Ther. (2004) [Pubmed]
  29. Baicalein inhibition of oxidative-stress-induced apoptosis via modulation of ERKs activation and induction of HO-1 gene expression in rat glioma cells C6. Chen, Y.C., Chow, J.M., Lin, C.W., Wu, C.Y., Shen, S.C. Toxicol. Appl. Pharmacol. (2006) [Pubmed]
  30. Bcl2 and ROS1 expression in human meningiomas: an analysis with respect to histological subtype. Girish, V., Sachdeva, N., Minz, R.W., Radotra, B., Mathuria, S.N., Arora, S.K. Indian journal of pathology & microbiology. (2005) [Pubmed]
  31. New Approach in The Treatment of T2DM and Metabolic Syndrome (Focus on a Novel Insulin Sensitizer). Tjokroprawiro, A. Acta medica Indonesiana (2006) [Pubmed]
  32. Neuroprotection conferred by astrocytes is insufficient to protect animals from succumbing to Japanese encephalitis. Mishra, M.K., Koli, P., Bhowmick, S., Basu, A. Neurochem. Int. (2007) [Pubmed]
  33. Regional localization of the human c-ros-1 on 6q22 and flt on 13q12. Satoh, H., Yoshida, M.C., Matsushime, H., Shibuya, M., Sasaki, M. Jpn. J. Cancer Res. (1987) [Pubmed]
  34. Prolongation of alloskin graft survival by catalytic scavengers of reactive oxygen species. Tocco, G., Illigens, B.M., Malfroy, B., Benichou, G. Cell. Immunol. (2006) [Pubmed]
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