Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epidermal growth factor receptor, EGFR, has been implicated in cell transformation in both mammalian and avian species. The v-ErbB oncoprotein is an oncogenic form of the chicken EGFR. The tyrosine kinase activity of this oncoprotein is required for transformation, but no transformation-specific cellular substrates have been described to date. Recently activation of the ras signal transduction pathway by the EGFR has been shown to involve the Shc and Grb2 proteins. In this communication, we demonstrate that the Shc proteins are phosphorylated on tyrosine residues and are complexed with Grb2 and the chicken EGFR following ligand activation of this receptor. In fibroblasts and erythroid cells transformed by the avian erythroblastosis virus (AEV) strains H and ES4, the Shc proteins are found to be constitutively phosphorylated on tyrosine residues. The tyrosine-phosphorylated forms of the AEV strain H v-ErbB protein are found in a complex with Shc and Grb2, but the Shc proteins do not bind to the AEV strain ES4 v-ErbB protein. Mutant forms of the v-ErbB protein (in which several of the tyrosines that become autophosphorylated have been deleted by truncation) are unable to transform erythroid cells but can still transform fibroblasts. Analysis of cells transformed by one of these mutants revealed that the truncated v-ErbB protein could no longer bind to either Shc or Grb2, but this oncoprotein still gave rise to tyrosine-phosphorylated Shc proteins that complexed with Grb2 and led to activation of mitogen-activated protein (MAP) kinase. The results suggest that stable binding of Grb2 and Shc to the v-ErbB protein is not necessary to activate this signal transduction pathway and assuming that the mutant activate MAP kinase in erythroid cells in a manner similar to that of fibroblasts, that activation of this pathway is not sufficient to transform erythroid cells.
 ...
PMID:Analysis of the role of the Shc and Grb2 proteins in signal transduction by the v-ErbB protein. 790 55

DNA probes for the NRAS, HRAS, KRAS2, LCK, RAF1, MET, MYCL1, MYCN, MYB, ERBB2, FOS, CSF1R, and SRC protooncogene loci; the retinoblastoma gene locus (RB1); the tumor virus integration sites INT2, PVT1, and MLV12; and the locus of the tumor-specific antigen T1A were used to screen mouse genomic DNAs from RF/J, CAST/Ei, MOLF/Ei, Mus musculus musculus, M. m. poschiavinus, and M. spretus. Polymorphic DNA fragments for the 18 DNA probes have been identified using Southern blot hybridization and restriction fragment length polymorphism (RFLP) analysis.
 ...
PMID:Novel RFLPs at protooncogene and cancer-related gene loci on mouse chromosomes. 809 10

Almost all atypical epithelial lesions of the stomach consist of atypical cells in the superficial part of the glands and nonatypical cells in the deeper portion of the glands. A transition zone was formed between the superficial atypical gland cells and the deeper nonatypical gland cells. Positive cells were widely demonstrated with immunohistochemical stains for PCNA in the superficial atypical glands and transition zone. The rate of PCNA positivity was 37.7%. However, a small number of positive cells for EGFR (8.5%), c-erbB-2(11.3%), p53(11.3%) and c-K-ras(1.7%) were found in ATP. The incidence of positivity for these factors was low compared with that for carcinomas. The percentages of positive cells for EGFR(1.5%) and c-erbB-2(4.5%) were very low in intestinal metaplasia.
 ...
PMID:[Immunohistochemical study for growth factor and oncogene on atypical epithelium of the stomach]. 810 26

Cancer has been defined as a fundamental disorder of cellular growth control. Which arises in some cells through changes in genes (DNA-level: geneamplification, mutation and rearrangement) or their expression (RNA- and protein-level), and gives these cells a growth advantage in comparison to the surrounding cells. Since the last decade we know the identity of these genes and the nature of the changes they underwent in the cancer cell. Only a few of the known oncogenes play a role in head and neck cancer. These are the EGFR (epidermal growth factor receptor), c-myc, the ras gene family, int-2, hst- 1 and bcl- 1. In some clinical disorders, like childhood neuroblastoma and breast cancer, oncogenes play already an important role in tumor staging as well as a prognostic parameter. The aim for the future is the therapeutic application of oncogenes better known as gene therapy.
 ...
PMID:Oncogenes related to head and neck cancer. 813 94

Net overexpression or derangements of PTK-encoding oncogenes and ras serve as critical driving forces in the evolution of many epithelial and lymphohematopoietic cancers. The ability to impede signal transduction through ras-based pathways could provide a powerful molecular target for therapy and prevention of a broad spectrum of malignant neoplasms.
 ...
PMID:Oncology and hematology. 818 56

Mitogen-activated protein kinases, MAP kinases or ERKs (extracellular signal-regulated kinases) are rapidly stimulated by growth-promoting factors acting on a variety of cell-surface receptors. In turn, ERKs phosphorylate and regulate key intracellular enzymes and transcription factors involved in the control of cellular proliferation. The tyrosine-kinase class of growth-factor receptors transmits signals to ERKs in a multistep process that involves Ras and a limited number of defined molecules. In contrast, ERK activation by G-protein-coupled receptors is poorly understood, as is the role of ras in this signalling pathway. We have explored in COS-7 cells the mechanism of ERKs activation by m1 and m2 muscarinic receptors, typical examples of receptors coupled through Gq proteins to induce phosphatidylinositol hydrolysis and to G(i) proteins to inhibit adenylyl cyclase, respectively. Here we present evidence that ERK activation is mediated by beta gamma subunits of heterotrimeric G proteins acting on a ras-dependent pathway.
 ...
PMID:Ras-dependent activation of MAP kinase pathway mediated by G-protein beta gamma subunits. 819 62

In order to examine whether the expression of the oncoproteins might be important for the malignancy of tumors, the relationship between the take rate of 88 human squamous cell lung carcinomas in nude mice and the expression of protooncogene products was analyzed. The expression of c-fos, c-jun, c-ras, c-erbB1, c-neu and c-myc at the protein level was investigated by immunohistochemistry. Tumor take was assumed if within three months growing nodules were detected and confirmed histologically. The take rate of squamous cell lung carcinomas in nude mice was 49%. Sixty-eight percent of the tumors were positive for Fos, 40% for Jun, 67% for Ras, 77% for ErbB1, 35% for Neu and 39% for Myc. Tumors with an (over)expression of the proteins encoded by the oncogenes c-fos, c-jun, c-erbB1 and c-ras had a significantly higher take rate in nude mice than tumors without an (over)expression of the oncogene products. In contrast, the expression of the c-neu and the c-myc genes at the protein level had no influence on the take rate of the tumors in nude mice. Interestingly, only patients with tumors with an (over)expression of the proteins encoded by the oncogenes c-fos, c-jun, c-erbB1 and c-ras had significantly shorter survival times than patients whose tumors did not show an (over) expression of the oncogene products. These results demonstrate that the aggressiveness of the tumors visible in the higher take rate of the tumors in nude mice and in the shorter survival times of patients can be detected by measurement of the expression of c-fos, c-jun, c-erbB1 and c-ras at the protein level.
 ...
PMID:Correlation between successful heterotransplantation of lung tumors in nude mice, poor prognosis of patients and expression of Fos, Jun, ErbB1, and Ras. 829 9

About 80% of neoplasias are epithelial in origin and, as such, understanding the molecular mechanisms involved in the development of epithelial tumours is vital to the diagnosis, prognosis and treatment of the vast majority of human cancers. Obviously this is no easy task but, as outlined above, great efforts are being made to identify important molecules involved in the progression of normal epithelial cells to carcinoma. The development of techniques to identify new oncogenes is of particular importance, and hopefully the cDNA expression cloning system of Stuart Aaronson will be a useful tool in this respect. The potential of some of these molecules to be used as therapeutic targets will require the development of suitable screening procedures, such as that being established by Chris Marshall for the ras-Map kinase pathway in yeast. It is encouraging that the immune response to virally (HPV) induced cancer is being carefully elucidated and the prospects of vaccine development for the treatment of cervical cancer coming nearer since this particular form of SCC is a major cancer globally. Finally it was fitting to end the meeting on an optimistic note with John Mendelsohn's EGFR monoclonal antibody therapy entering clinical trials, and hopefully this will prove efficacious in the treatment of human SSC.
 ...
PMID:1st international Beatson symposium--cellular, molecular and clinical aspects of squamous cell carcinomas. 829 43

Hepatocyte Growth Factor (HGF) and Scatter Factor (SF) are identical glycoproteins secreted by cells of mesodermal origin. The factor has several activities on epithelial cells, including mitogenesis, dissociation of epithelial sheets, stimulation of cell motility, and promotion of matrix invasion. HGF is the ligand for p190MET, the receptor tyrosine kinase encoded by the MET proto-oncogene. This was proved by HGF binding to immunopurified p190MET, chemical cross-linking of radiolabelled ligand, HGF-induced tyrosine phosphorylation of p190MET, and reconstitution of high-affinity binding sites for HGF into insect cells infected with a recombinant baculovirus carrying the human MET cDNA. p190MET is a 190 kDa heterodimer of two (alpha beta) disulfide-linked protein subunits. The alpha subunit is heavily glycosylated and extracellular. The beta subunit bears an extracellular portion involved in ligand binding, a membrane spanning segment and a cytoplasmic tyrosine kinase domain with phosphorylation sites regulating its activity. Both subunits originate from glycosylation and proteolytic cleavage of a common precursor of 170 kDa. Alternative post-transcriptional processing originates two truncated Met proteins, endowed with ligand binding activity, lacking the cytoplasmic kinase domain of the beta subunit. One form is soluble and released from the cells. HGF binding triggers tyrosine autophosphorylation of the receptor beta subunit in intact cells. Autophosphorylation upregulates the kinase activity of the receptor, increasing the Vmax of the phosphotransfer reaction. The major phosphorylation site has been mapped to Tyr1235. Negative regulation of the receptor kinase activity occurs through distinguishable pathways involving protein kinase C activation or increase in the intracellular Ca2+ concentration. Both lead to the serine phosphorylation of a unique phosphopeptide of the receptor and to a decrease in its kinase activity. Receptor autophosphorylation also triggers the signal transduction pathways inside the target cells. The phosphorylated receptor associates ras GAP, phospholipase C-gamma, and src-related tyrosine kinase in vitro; Phosphatidylinositol 3-kinase, in vitro and in vivo, indicating that the generation of the D-3 phosphorylated inositol lipids is involved in effecting the motility and/or the growth response to HGF. The p190MET HGF receptor is expressed in several epithelial tissues and it is often overexpressed in neoplastic cells. In some tumors of the gastrointestinal tract the Met tyrosine kinase is constitutively activated, either by overexpression of the amplified MET oncogene or by lack of cleavage of the receptor precursor, due to defective post-translational processing.
 ...
PMID:Structure, biosynthesis and biochemical properties of the HGF receptor in normal and malignant cells. 838 Jul 35

Non-small cell lung carcinoma specimens of 173 previously untreated patients were analyzed for the expression of proteins encoded by the oncogenes c-myc, c-fos, c-jun, c-erbB-1, c-erbB-2, c-H-ras, c-K-ras and c-N-ras. Forty-six per cent of the tumors were positive for the c-MYC protein, 60% for c-FOS, 50% for c-JUN, 80% for c-ERBB-1, 55% for c-ERBB-2, 12% for c-H-RAS, 5% for c-K-RAS and 71% for c-N-RAS. Proteins encoded by c-fos and c-jun are overexpressed more frequently in carcinomas of smokers (c-fos: P < 0.005; c-jun: P < 0.01). When we grouped the patients according to their tumor histology the results became more evident. Squamous cell lung carcinomas of smokers showed a higher incidence of c-FOS (P = 0.01), c-JUN (P < 0.01) and c-ERBB-1 (P = 0.01) proteins than squamous cell lung carcinomas of non-smokers. The expression rate and the intensity of staining proved not to be influenced either by the number of cigarettes smoked daily or by cessation of smoking. In adenocarcinomas, however, we only found a trend for a more frequent overexpression of c-fos (P = 0.07) and c-jun (P = 0.14) encoded proteins in carcinomas of smokers and no correlation between the expression of c-erbB-1 products and smoking. No correlation was found between the expression of c-MYC, c-ERBB-2, c-H-RAS, c-K-RAS and c-N-RAS proteins and the smoking habits of the patients, neither in squamous cell carcinomas nor in adenocarcinomas of the lung.
 ...
PMID:Overexpression of oncoproteins in non-small cell lung carcinomas of smokers. 838 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>