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)

Hepatocyte growth factor (HGF), also known as scatter factor (SF), is a polypeptide which induces motility and/or mitogenesis in epithelial cells. The receptor for HGF/SF, p190MET, is a two-chain transmembrane tyrosine kinase encoded by the MET proto-oncogene. To identify the cytoplasmic effectors involved in signal transduction we have produced the human HGF/SF receptor in insect cells (Sf9) by means of a recombinant baculovirus. Two 170-kDa forms of the receptor were synthesized in Sf9 cells: the uncleaved single-chain precursor (which is by far the more abundant) and the proteolytically processed two-chain molecule. Both receptor species are phosphorylated on tyrosine in vivo and are active kinases in vitro. The recombinant receptor binds and phosphorylates in vitro four known cytoplasmic transducers containing src homology region 2 (SH2) domains: the 85-kDa subunit of phosphatidylinositol 3-kinase (Pl 3-kinase), rasGAP, phospholipase-C gamma (PLC-gamma), and p59Fyn, a tyrosine kinase of the src family. In all cases the association is strictly dependent on tyrosine phosphorylation of the receptor, indicating that it occurs via specific interaction with the SH2 domains. These results show that the HGF/SF receptor has the sequence requirements for binding a spectrum of cytoplasmic transducers whose different combinations in target cells may result in the observed pleiotropic biological response.
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PMID:Autophosphorylation promotes complex formation of recombinant hepatocyte growth factor receptor with cytoplasmic effectors containing SH2 domains. 132 86

The proto-oncogene c-MET encodes a transmembrane tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF). HGF/SF stimulates the proliferation and motility of various cell types. Because HGF/SF is also a melanocyte mitogen, we investigated the biological role of HGF/SF, including c-Met expression, activation and signal transduction, in normal and malignant human melanocytes. We show that HGF/SF is mitogenic in the presence of synergistic factors, such as basic fibroblast growth factor (bFGF) and mast cell growth factor (MGF) and that, by itself, it stimulates the motility of normal human melanocytes. The ligand also maintained high levels of tyrosinase activity and melanin content in theses cells. Signal transduction by HGF/SF included phosphorylation of tyrosyl residues on c-Met, a cascade of tyrosine phosphorylations on several other proteins and activation of microtubule-associated protein kinase/extracellular signal-regulated kinase. Met expression and activity are normal in human melanomas, and constitutive activity of HGF/SF in retrovirally infected autonomously proliferative mouse melanocytes is insufficient to confer the malignant phenotype. Our findings suggest that activation of Met in response to HGF/SF may contribute to malignant progression synergistically with the aberrant expression of bFGF in malignant melanocytes and that, in addition, the peptide may promote dispersion of factor-dependent melanocytes from early stages of primary melanomas to ectopic sites.
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PMID:Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells. 133 34

The receptor for Hepatocyte Growth Factor is a transmembrane tyrosine kinase encoded by the c-MET oncogene. We have previously shown that the Met protein is expressed in several human epithelial tissues. The receptor is barely detectable, however, in normal thyroids and in specimens from patients affected by non-neoplastic thyroid diseases. Now we report that the expression of the Met/HGF receptor is increased a hundred fold in 22 out of 41 human carcinomas derived from the thyroid follicular epithelium. A comprehensive analysis of 15 cases showed that the overexpressing carcinomas belong to histotype variants correlated with negative prognosis and in all but one case there were evidences of locally advanced disease and/or distant metastases. The 11 benign adenomas and the 5 medullary carcinomas tested were negative. Western blot analysis with monoclonal antibodies directed against either the intracellular or the extracellular receptor domains failed to reveal major structural alterations. Southern blot analysis also demonstrated that the c-MET gene was not amplified nor rearranged. These data suggest a role for the overexpression of c-MET oncogene in the pathogenesis and progression of thyroid tumors derived from the follicular epithelium.
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PMID:Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas. 133 53

The genes encoding the regulatory subunits RI beta (locus PRKAR1B) and RII beta (locus PRKAR2B) of human cAMP-dependent protein kinase have been mapped in the basic CEPH (Centre d'Etude du Polymorphisme Humain) family panel of 40 families to chromosome 7p and 7q, respectively, using the enzymes HindIII and BanII recognizing the corresponding restriction fragment length polymorphisms (RFLPs). Previous data from the CEPH database and our present RFLP data were used to construct a six-point local framework map including PRKAR1B and a seven-point framework map including PRKAR2B. The analysis placed PRKAR1B as the most distal of the hitherto mapped 7p marker loci and resulted in an unequivocal order of pter-PRKAR1B-D7S21-D7S108-D7S17-D7S149- D7S62-cen, with a significantly higher rate of male than female recombination between PRKAR1B and D7S21. The 7q regulatory gene locus, PRKAR2B, could also be placed in an unambigous order with regard to the existing CEPH database 7q marker loci, the resulting order being cen-D7S371-(COL1A2,D7S79)-PRKAR2B-MET-D7S87++ +-TCRB-qter. Furthermore, in situ hybridization to metaphase chromosomes physically mapped PRKAR2B to band q22 on chromosome 7.
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PMID:Mapping of the regulatory subunits RI beta and RII beta of cAMP-dependent protein kinase genes on human chromosome 7. 135 99

The 5-HT-2 antagonist ketanserin (KAS) has been successfully used to treat acute hypertension in coronary bypass surgery. The present study was performed to investigate the effect of KAS on ischaemic myocardium. In 11 anaesthetized (piritramide) dogs, systolic contraction (sdL) and end-diastolic length (edL) of myocardium supplied by the left descending coronary artery (LAD) and the left circumflex coronary artery (LCX) were measured by sonomicrometry simultaneously with aortic pressure (AoP), left ventricular dP/dtmax and end-diastolic pressure (LVedP), heart rate (HR), stroke volume, and LAD flow (QLAD). Regional ischaemia to decrease sdLLAD (-48%) was achieved by LAD stenosis (QLAD -47%). Concomitantly, edLLAD increased by 8%. However, the other variables did not change. Then KAS was given i.v. (0.15 + 0.15 + 0.30 + 0.6 mg/kg) at 15-min intervals. Following KAS, prestenotic sdLLAD recovered in a dose-dependent manner. LVedP and edLLAD decreased, sdLLCX increased, and the other variables were not affected. This functional recovery of ischaemic myocardium was attenuated by pretreatment with metoprolol (MET, 1 mg/kg) prior to LAD stenosis. The ischaemic area was not irreversibly damaged, however, as proven by the recovery of prestenotic sdLLAD values after release of the stenosis. The improved systolic shortening of ischaemic myocardium following KAS did not result from restored QLAD due to post-stenotic vasodilation or break up of platelet aggregates (QLAD did not increase) or from reduced afterload (AoP did not decrease). Obviously, it was mediated by beta-1-receptors, as shown by the attenuation of the beneficial effect of KAS by pretreatment with MET.
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PMID:Effects of the serotonin-antagonist ketanserin on the function of ischaemic and normally perfused myocardium and modification by beta-1-blockade in anaesthetized normotensive dogs. 135 17

Hepatocyte Growth Factor (HGF, also known as Scatter Factor) is a powerful mitogen or motility factor in different cells, acting through the tyrosine kinase receptor encoded by the MET protooncogene. Endothelial cells express the MET gene and expose at the cell surface the mature protein (p190MET) made of a 50 kD (alpha) subunit disulfide linked to a 145-kD (beta) subunit. HGF binding to endothelial cells identifies two sites with different affinities. The higher affinity binding site (Kd = 0.35 nM) corresponds to the p190MET receptor. Sub-nanomolar concentrations of HGF, but not of a recombinant inactive precursor, stimulate the receptor kinase activity, cell proliferation and motility. HGF induces repairs of a wound in endothelial cell monolayer. HGF stimulates the scatter of endothelial cells grown on three-dimensional collagen gels, inducing an elongated phenotype. In the rabbit cornea, highly purified HGF promotes neovascularization at sub-nanomolar concentrations. HGF lacks activities related to hemostasis-thrombosis, inflammation and endothelial cells accessory functions. These data show that HGF is an in vivo potent angiogenic factor and in vitro induces endothelial cells to proliferate and migrate.
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PMID:Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. 138 37

A study of the adhesive interface between 4-MET/MMA-TBB resin and hydroxyapatite or bovine enamel was reported. The present report is a continuation of that study. The possible chemical interaction between 4-methacryloxyethyl trimellitic acid (4-MET) and bovine or human dentin was examined by laser Raman spectroscopy. A 4-MET monomer solution was prepared by evaporating two thirds of the methyl methacrylate (MMA) in a commercial dentin adhesive. The solution was then applied to a dentin surface after treating the surface with an aqueous solution of 10% citric acid containing 3% ferric chloride. A salt formed on both bovine and human dentin surfaces. This salt was formed by the process we previously reported in which 4-MET formed a salt on the hydroxyapatite and bovine enamel. No evidence was observed of chemical reaction between 4-MET and any organic component in the dentin.
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PMID:Laser-Raman spectroscopic study of the adhesive interface; analysis between 4-META/MMA-TBB resin and bovine or human dentin. 139 87

We hypothesized that the prediction of physical activity from psychological determinants would differ when free-living physical activity was assessed by electromechanical or self-report methods. We assessed outcome-expectancy values and perceived barriers for physical activity (OE Values/P Barriers) and physical self-efficacy in 44 young (24 yr +/- 4.8) Caucasian men (N = 13) and women (N = 31). Two weeks later, subjects kept a daily diary and wore a Caltrac motion sensor during all ambulation for seven consecutive days. Reliability (PI) across days was high for MET.h of activity estimated by the diary (0.82) and for Caltrac counts (0.87). Canonical correlation analysis yielded one significant linear combination (Rc = 0.55, P less than 0.01; redundancy = 0.19 to 0.24) of the set of psychological variables [OE Values/P Barriers (beta = 0.76) and physical self-efficacy (B = 0.33)] and the set of physical activity estimates [7-d diary (B = 0.89) and Caltrac (beta = 0.24)]. Multiple correlations indicated that the linear combination of OE Values/P Barriers and physical self-efficacy explained 26% of the variation in MET.h reported in the 7-d diary (P less than 0.01) but was unrelated to Caltrac counts (P greater than 0.05). The strongest bivariate model included the 7-d diary and OE Values/P Barriers (r = 0.51, P less than 0.01). Caltrac counts were weakly related to OE Values/P Barriers (r = 0.34, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Failure to generalize determinants of self-reported physical activity to a motion sensor. 140 76

The purposes of this study were to evaluate (a) the effects of step rate and upper body support on the VO2 and HR responses to fixed work rates on the StairMaster 4000 (SM), (b) the accuracy of the SM settings, and (c) how HR compared with that measured during grade-walking on a treadmill. Six subjects worked at a slow step rate for 6 min and then a faster step rate for the last 6 min of a 12-min test at SM settings of 4, 7, and 10 METs. Gas exchange and HR measurements were made at minutes 4-6 and 10-12. Variations in step rate had no effect on HR (P = 0.45) or VO2 (P = 0.84). The effect of using the arms and hands for support was studied using 6 subjects who worked for 12 min at 4, 7, and 10 METs; the first 6 min without support, and the second 6 min with support. Support resulted in lower HR (P = 0.017) and VO2 (P = 0.002) values at 10 METs. The measured MET values were about 20% lower than those specified by machine settings: True MET values = 0.556 + 0.745 (SM setting). Finally, at the same VO2, systematically higher (7-11 b.min-1) HR values were observed for the SM relative to the treadmill.
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PMID:Factors affecting the oxygen cost of stepping on an electronic stepping ergometer. 140 90

A diapause associated protein was electrophoretically isolated from the hemolymph of diapausing last instar larvae of the pink bollworm Pectinophora gossypiella. This protein (M(r) approximately 490,000, glycolipoprotein) was given the name Pectinophora diapause protein (PDP). It is composed of one subunit (M(r) 103,000). The concentration of PDP increased dramatically in the hemolymph of diapausing larvae from 17.4% in prediapause (PD) phase to 29.2% in early diapause (ED) phase reaching a level of 38.6% in larval hemolymph of middiapause (MD) phase. The concentrations of total proteins in the hemolymph of active feeding (A), PD, ED, and MD larvae were 69.8, 106,6, 113.3, and 118 mg/ml, respectively, while those in the fat body of the same larvae were 7.1, 7.4, 8.8, and 4.5 mg/g, respectively. In Pectinophora a drop in the concentration of fat body proteins coincided with a corresponding increase in hemolymph proteins, which suggests an active release of protein from the fat body into the hemolymph during the development of diapause. A partial amino acid sequence of pectinophorin showed the first 15 amino acids starting from the amino terminus of the peptide chain: N-ALA-LYS-THR-ILEU-VAL-GLU-ASN-MET-PRO-PRO-THR-PRO-LEU-ASN-ALA-C.
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PMID:A diapause associated protein of the pink bollworm Pectinophora gossypiella Saunders. 142 41


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