Disease relevance of ROS1

• Expression and rearrangement of the ROS1 gene in human glioblastoma cells [1].
• We isolated a human gene (designated c-ros-1) homologous to the v-ros sequence of UR2 sarcoma virus [2].
• TNFalpha induces chromosomal abnormalities independent of ROS through IKK, JNK, p38 and caspase pathways [3].
• CAGE, a novel cancer/testis antigen gene, promotes cell motility by activation ERK and p38 MAPK and downregulating ROS [4].
• ROS1 was expressed at high levels in approximately 55% (17 of 31) of the meningiomas examined, but not expressed in non-neoplastic brain samples [5].

Psychiatry related information on ROS1

• Unraveling the molecular mechanisms affected by ROS/RNS acting in these capacities should aid in the understanding of how stimulated defense mechanisms within the airway can lead to disease [6].
• Oxidative stress, reactive oxygen (ROS), and nitrogen (RNS) species have been known to be involved in a multitude of neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) [7].
• The present study demonstrates that Myoinositol/folic acid combination, deserves consideration as therapeutic agent for preventing and treating erectile dysfunction in diabetic men, probably by virtue of both their chronic metabolic, acute ROS scavenging, and NO protective beneficial effects [8].

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

• Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21) [13].
• Increased stability of P21(WAF1/CIP1) mRNA is required for ROS/ERK-dependent pancreatic adenocarcinoma cell growth inhibition by pyrrolidine dithiocarbamate [14].
• Comparing two rat osteogenic sarcoma cell lines, one that produces constitutively relatively high levels of the 1,25-(OH)2D3 receptor protein (ROS 17/2.8) and one in which the 1,25-(OH)2D3 receptor protein is practically undetectable (ROS 2/3), we found that the 1,25-(OH)2D3 receptor-expressing cell line also expressed c-myc mRNA [15].
• The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status [16].
• To study regulation of the parathyroid hormone (PTH)-responsive adenylate cyclase of osteoblast-like cells by 1,25-dihydroxyvitamin D (1,25(OH)2D), cAMP levels and adenylate cyclase activity were assayed in the hormone-responsive ROS 17/2.8 rat osteosarcoma cell line [17].

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

• We have regionally localized the two human tyrosine kinase proto-oncogenes, c-ros-1 and flt, by in situ hybridization [33].
• Immunoprecipitation analysis reveals that the U-118 MG expressed a smaller, 116 kD ros1 gene product. cDNA cloning and sequencing of the U-118 MG ros1 transcript indicates it encodes the entire tyrosine kinase domain and two amino acids of the transmembrane domain of ros1 at its 3' end [27].
• Expression of the ROS1 oncogene, a member of the receptor tyrosine kinase superfamily, was examined in human meningiomas by coupled reverse transcription and polymerase chain reaction (RT-PCR) assays [5].
• Two sets of region-specific oligonucleotides, specific for different regions of the ROS1 messenger ribonucleic acid (mRNA), were used in RT-PCR assays to independently examine ROS1 transcripts from primary human meningiomas [5].
• Our results indicate that salen manganese complexes mediate their effect on graft rejection both by reducing the susceptibility of graft tissue to ROS-mediated injury and by exerting an anti-inflammatory effect in recipients [34].

References