Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The candidate tumor-suppressor gene hyaluronidase 2 (HYAL2) encodes a glycosylphosphatidylinositol-anchored cell-surface protein that serves as an entry receptor for jaagsiekte sheep retrovirus, a virus that causes contagious lung cancer in sheep that is morphologically similar to human bronchioloalveolar carcinoma. The viral envelope (Env) protein alone can transform cultured cells, and we hypothesized that Env could bind and sequester the HYAL2 receptor and thus liberate a potential oncogenic factor bound and negatively controlled by HYAL2. Here we show that the HYAL2 receptor protein is associated with the RON receptor tyrosine kinase (also called MST1R or Stk in the mouse), rendering it functionally silent. In human cells expressing a jaagsiekte sheep retrovirus Env transgene, the Env protein physically associates with HYAL2. RON liberated from the association with HYAL2 becomes functionally active and consequently activates the Akt and mitogen-activated protein kinase pathways leading to oncogenic transformation of immortalized human bronchial epithelial cells. We find activated RON in a subset of human bronchioloalveolar carcinoma tumors, suggesting RON involvement in this type of human lung cancer.
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PMID:Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus. 1267 86

The cytokine Macrophage Stimulating 1 (MST1/MSP/Hepatocyte Growth Factor-Like) is a ligand of the Met-related MST1-Receptor (MST1R/RON). Although MST1-deficient mice are viable, MST1R is essential in mice before gastrulation for implantation, and is a known oncogene in man. Here I report the identification, sequence, chromosomal location and embryonic expression of a novel zebrafish orthologue, termed macrophage stimulating 1 (mst1). mst1 shows a striking restriction of expression to the dorsal side of the embryo prior to gastrulation, and as gastrulation and somitogenesis proceed is expressed sequentially in the presumptive neurectoderm, the notochord, the somites, endodermal cells and in the syncytial yolk. This dynamic pattern is largely conserved in tetrapod vertebrates, suggesting that the appearance of MST1, may have played an early role in the evolution of the vertebrate body plan.
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PMID:Identification and developmental expression of a macrophage stimulating 1/ hepatocyte growth factor-like 1 orthologue in the zebrafish. 1276 15

Macrophage-stimulating protein (MSP) promotes the phagocytosis of C3bi-coated erythrocytes by resident peritoneal macrophages, although the mechanism by which this occurs is largely unknown. We show that MSP-induced complement-mediated phagocytosis requires the RON receptor tyrosine kinase and the alphaMbeta2 integrin, as evidenced by the inability of RON-/- and alphaM-/- peritoneal macrophages to augment phagocytosis of complement-coated sheep erythrocytes in response to MSP. MSP stimulation of macrophages results in tyrosine phosphorylation and AKT activation, and inhibitor studies demonstrate a phagocytic requirement for tyrosine kinase and phosphatidylinositol 3-kinase (PI-3K) activity as well as activity of the atypical protein kinase C (PKC) isoform zeta, which localizes to MSP-induced phagosomes containing complement-coated beads. Additionally, MSP augments the ability of peritoneal macrophages to bind to intercellular adhesion molecule-1 (ICAM-1) via the alphaMbeta2 integrin. MSP-induced ICAM-1 adhesion is also dependent on tyrosine kinase activity, PI-3K, and PKC zeta, indicating that these signaling requirements are upstream of complement receptor 3 activation.
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PMID:Activation of CR3-mediated phagocytosis by MSP requires the RON receptor, tyrosine kinase activity, phosphatidylinositol 3-kinase, and protein kinase C zeta. 1277 13

The MST1R (RON) gene, that maps at 3p21.3, encodes a protein tyrosine kinase receptor comprised of an extra-cellular domain that contains the ligand binding pocket and an intracellular region where the kinase domain is located. It controls cell survival and motility programs related to invasive growth. With the single strand conformation polymorphism (SSCP) method, a C to A nucleotide polymorphism (SNP) was found in intron 18 of the gene. The SNP has a frequency of 0.28 among African-American, 0.25 among Caucasian CEPH and 0.09 among Asian healthy individuals. During these studies, an alternatively spliced cDNA of MST1R, lacking exon 19, was also found that may result from this change.
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PMID:C to A single nucleotide polymorphism in intron 18 of the human MST1R (RON) gene that maps at 3p21.3. 1278 25

The product of the RON (recepteur d'origine nantais) gene belongs to the MET proto-oncogene family, a distinct subfamily of receptor tyrosine kinases. The ligand of RON was identified as macrophage-stimulating protein (MSP), a member of the plasminogen-related growth factor family. RON is mainly expressed in cells of epithelial origin and is required for embryonic development. In vitro RON activation results in epithelial cell dissociation, migration and matrix invasion, suggesting that RON might be involved in the pathogenesis of certain epithelial cancers in vivo. Indeed, recent studies have shown that RON expression is significantly altered in several primary human cancers, including those of the breast and colon. Truncation of the RON protein has also been found in primary tumors from the gastrointestinal tract. These alterations lead to constitutive activation of RON that causes cell transformation in vitro, induces neoplasm formation in athymic nude mice, and promotes tumor metastasis into the lung. Studies employing transgenic models further demonstrated that over-expression of RON in lung epithelial cells results in multiple tumor formation with features of large cell undifferentiated carcinoma. The oncogenic activities of RON are mediated by RON-transduced signals that promote unbalanced cell growth and transformation leading to tumor development. Thus, abnormal accumulation and activation of RON could play a critical role in vivo in the progression of certain malignant human epithelial cancers.
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PMID:Oncogenic and invasive potentials of human macrophage-stimulating protein receptor, the RON receptor tyrosine kinase. 1280 33

RON is a member of the receptor tyrosine kinase gene family that includes the MET oncogene, whose germline mutations have been causally related to human tumorigenesis. In vitro, RON and MET receptors cross-talk, synergize in intracellular signaling, and cooperate in inducing morphogenic responses. Here we show that the RON and MET oncogenes were expressed in 55% and 56% of human ovarian carcinomas, respectively, and were significantly coexpressed in 42% (P < 0.001). In ovarian carcinoma samples and cell lines we did not find mutations in RON and MET gene kinase domain, nor coexpression of RON and MET receptor ligands (MSP and HGF, respectively). We show that motility and invasiveness of ovarian cancer cells coexpressing MET and RON receptors were elicited by HGF and, to a lesser extent, by MSP. More interestingly, invasion of both reconstituted basement membrane and collagen gel was greatly enhanced by the simultaneous addition of the two ligands. These data suggest that coexpression of the MET and RON receptors confer a selective advantage to ovarian cancer cells and might promote ovarian cancer progression.
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PMID:The RON and MET oncogenes are co-expressed in human ovarian carcinomas and cooperate in activating invasiveness. 1291 29

A life cycle assessment has been done to compare the potential environmental impacts of various gasoline blends that meet octane and vapor pressure specifications. The main blending components of alkylate, cracked gasoline, and reformate have different octane and vapor pressure values as well as different potential environmental impacts. Because the octane and vapor pressure values are nonlinearly related to impacts, the results of this study show that some blends are better for the environment than others. To determine blending component compositions, simulations of a reformer were done at various operating conditions. The reformate products of these simulations had a wide range of octane values and potential environmental impacts. Results of the study indicate that for low-octane gasoline (95 Research Octane Number), lower reformer temperatures and pressures generally decrease the potential environmental impacts. However, different results are obtained for high-octane gasoline (98 RON), where increasing reformer temperatures and pressures increase the reformate octane values faster than the potential environmental impacts. The higher octane values for reformate allow blends to have less reformate, and therefore high-octane gasoline can have lower potential environmental impacts when the reformer is operated at higher temperatures and pressures. In the blends studied, reformate and cracked gasoline have the highest total impacts, of which photochemical ozone creation is the largest contributor (assuming all impact categories are equally weighted). Alkylate has a much lower total potential environmental impact but does have higher impact values for human toxicity by ingestion, aquatic toxicity, terrestrial toxicity, and acidification. Therefore, depending on environmental priorities, different gasoline blends and operating conditions should be chosen to meet octane and vapor pressure specifications.
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PMID:Life cycle assessment of gasoline blending options. 1295 87

RON is a receptor tyrosine kinase of the MET family that is involved in cell proliferation, cell survival, and cell motility in both normal and disease states. Macrophage-stimulating protein (MSP) is the RON ligand whose binding to RON causes receptor activation. RON is a trans-membrane heterodimer comprised of one alpha- and one beta-chain originating from a single-chain precursor and held together by several disulfide bonds. The intracellular part of RON contains the kinase domain and regulatory elements. The extracellular region is characterized by the presence of a sema domain (a stretch of approximately 500 amino acids with several highly conserved cysteine residues), a PSI (plexin, semaphorins, integrins) domain, and four immunoglobulin-like folds. Here we show that a soluble, secreted molecule representing the sema domain of RON (referred to as ron-sema) has a dominant negative effect on the ligand-induced receptor activation and is capable of inhibiting RON-dependent signaling pathways and cellular responses. Results suggest that the sema domain of RON participates in ligand binding by the full-length receptor. The ability of ron-sema to suppress growth of MSP-responsive cells in culture, including cancer cells, points to a potential therapeutic use of this molecule, and forced expression of it could potentially be used as a gene therapy tool for treating MSP-dependent types of cancer.
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PMID:The soluble sema domain of the RON receptor inhibits macrophage-stimulating protein-induced receptor activation. 1459 39

Erythropoietin (EPO) is required for cell survival during differentiation and for progenitor expansion during stress erythropoiesis. Although signaling pathways may couple directly to docking sites on the EPO receptor (EpoR), additional docking molecules expand the signaling platform of the receptor. We studied the roles of the docking molecules Grb2-associated binder-1 (Gab1) and Gab2 in EPO-induced signal transduction and erythropoiesis. Inhibitors of phosphatidylinositide 3-kinase and Src kinases suppressed EPO-dependent phosphorylation of Gab2. In contrast, Gab1 activation depends on recruitment and phosphorylation by the tyrosine kinase receptor RON, with which it is constitutively associated. RON activation induces the phosphorylation of Gab1, mitogen-activated protein kinase (MAPK), and protein kinase B (PKB) but not of signal transducer and activator of transcription 5 (Stat5). RON activation was sufficient to replace EPO in progenitor expansion but not in differentiation. In conclusion, we elucidated a novel mechanism specifically involved in the expansion of erythroblasts involving RON as a downstream target of the EpoR.
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PMID:Tyrosine kinase receptor RON functions downstream of the erythropoietin receptor to induce expansion of erythroid progenitors. 1498 82

A method for predicting "octane numbers" (RON and MON) in fluid catalytic cracking (FCC) gasolines is proposed. Using FT-MIR and PLS, improvements have been obtained in sample throughput, reduced delay times, accuracy (repeatability and reproducibility), amounts of samples and reagents and environmental working conditions when compared with current standard methods. A total number of 140 daily production samples were taken; and from there, a learning group was prepared (44 samples); a validation set (96 samples) was prepared, as well. Sample spectra were recorded from 4000 to 600 cm(-1) at 4 cm(-1) intervals (traditional sealed NaCl cells). The PLS technique was used in its two variants (1 and 2-block). Both provided similar results. Their predictive characteristics are very good: SEP(RON)=0.38; SEP(MON)=0.40; repeatability <0.1 O.N.; reproducibility <0.3 O.N. (SEP=Standard Error of Prediction).
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PMID:Prediction of FCC gasoline octane numbers using FT-MIR and PLS. 1504 54


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