Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nature and role of cell surface proteins that bind members of the TGF-beta family has been investigated. TGF-beta, activins, and BMPs each bind to receptors of 55 kDa (type I) and 70 kDa (type II). In the TGF-beta system, these receptors are implicated in the mediation of multiple responses. A member of the type II receptor family has been cloned that encodes four alternatively spliced versions of a transmembrane serine/threonin kinase receptor related to the recently cloned mouse activin receptor and C-elegans daf-1 gene. Inhibitors of serine/threonine kinase activity block transcriptional and growth inhibitory responses to TGF-beta. In addition to the signaling receptors, many cell types express the TGF-beta binding proteoglycan betaglycan. Betaglycan has been purified, molecularly cloned, and shown to bind TGF-beta via its core protein and basic fibroblast growth factor via its heparan sulfate chains. In addition to receptors I and II and betaglycan, some cells express a newly identified set of membrane proteins that specifically bind either TGF-beta 1 or TGF-beta 2. Three of the four isoform-restricted binding proteins are bound to the membrane via phospholipid anchors. Like betaglycan, these proteins might function to regulate the interaction between TGF-beta and their target cells.
Mol Reprod Dev 1992 Jun
PMID:TGF-beta receptors. 132 48

A novel, simple, rapid, sensitive and reproducible microassay is described for determination of myoglobin and hemoglobin content of myocardial and skeletal muscle biopsy specimens from various mammals, birds and fish. As little as 50 mg of tissue is needed and myoglobin concentrations lower than 1 mg% can be detected. Myoglobin and hemoglobin are separated at alkaline pH by ammonium sulfate extraction followed by ultrafiltration. Heme content is determined by absorption of the Soret band when the hemoprotein extract is visibly colored or more sensitively by its peroxidase activity when the extract has low color. The heme reacts with tertiary-butyl hydroperoxide and orthotolidine to generate a blue color. Hemoglobin content is correlated with myoglobin content and is related to aerobic capacity and blood flow to the tissue. Myoglobin content varied over 5 orders of magnitude up to 7 per cent of the weight of tissue, whereas hemoglobin content varied over 2 orders of magnitude up to 6 per cent of tissue weight. Myoglobin content is increased in species with high basal metabolic rate, high physical activity, prolonged diving capacity, fatigue resistance, and red muscle, whereas it is decreased in white muscle, iron-deficient animals, animals with sedentary lifestyles, and in animals and tissues with small fiber diameters such as avian or fish hearts.
Mol Cell Biochem 1992 May 13
PMID:Rapid, simple and sensitive microassay for skeletal and cardiac muscle myoglobin and hemoglobin: use in various animals indicates functional role of myohemoproteins. 132 34

Chronic treatment with reserpine (0.1 mg/kg/day x 7 days) leads to the development of adaptive supersensitivity of ventricular myocardium of guinea pigs. The compensatory increase in sensitivity is associated with a small increase in beta-adrenoreceptor number. However, sensitivity is increased to a number of agonists that do not interact with beta-adrenoceptors. An evaluation of the role of both adenylyl cyclase and guanine nucleotide-binding regulatory proteins in the development of adaptive supersensitivity was carried out using crude membrane fragments from untreated control and chronically reserpine-treated guinea pigs. Quantitative analysis of Gs alpha and Gi protein concentrations was accomplished using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Chronic treatment with reserpine reduced basal levels of adenylyl cyclase activity by nearly 60%. The reduced activity was not the result of a loss of endogenous norepinephrine, because incubation of tissues in the presence of propranolol did not alter the basal level of adenylyl cyclase activity. Incubation in the presence of guanylylimido diphosphate (10(-5) M) also significantly reduced basal adenylyl cyclase activity, by nearly 70%. Chronic treatment with reserpine failed to significantly alter the activation of adenylyl cyclase by isoproterenol, impromidine, NaF, or forskolin. These data suggest that chronic treatment with reserpine does not alter agonist-induced activation of adenylyl cyclase. Furthermore, analysis of Gs alpha and Gi indicated that chronic treatment with reserpine did not affect the levels of these regulatory proteins in ventricular myocardial membranes. The data indicate that the enhanced sensitivity of guinea pig ventricular myocardium is not the result of an alteration in adenylyl cyclase activity or in the concentration of guanine nucleotide regulatory proteins. Therefore, the enhanced responsiveness to widely diverse agonists must be due to an alteration in cellular function beyond the level of adenylyl cyclase.
Mol Pharmacol 1992 Nov
PMID:Adenylyl cyclase and guanine nucleotide-binding proteins in supersensitive guinea pig ventricles. 133 61

Inorganic pyrophosphate-dependent phosphofructokinase was identified in toxoplasma gondii and purified to near homogeneity from the crude extracts. The purified enzyme displayed one major protein band which coincided with enzyme activity on nondenaturing polyacrylamide gel electrophoresis. This phosphofructokinase had a molecular weight of 100,000 determined by gel filtration and was composed of one type of subunit with the molecular weight of 45,000 estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting that the enzyme is a homodimer. Some kinetic parameters of the purified enzyme were investigated in the forward and the reverse directions. The substrate saturation curves for fructose 6-phosphate and pyrophosphate were all hyperbolic. The apparent Km values for fructose 6-phosphate and for pyrophosphate were 2.7 x 10(-4) M and 3.3 x 10(-5) M respectively. Kinetics for Fru-1,2-P2 and for Pi in the reverse reaction were also hyperbolic. The activity of this enzyme was magnesium-dependent. Nucleoside triphosphates and polyphosphates did not serve as phosphate donor and the enzyme activity was not altered in the presence of any of these nucleotides. As in the case of pyrophosphate-dependent phosphofructokinases from other anaerobic eukaryotes the Toxoplasma enzyme was not activated by fructose 2,6-biphosphate.
Mol Biochem Parasitol 1992 Sep
PMID:Purification and properties of a pyrophosphate-dependent phosphofructokinase from Toxoplasma gondii. 133 84

Transforming growth factor-beta (TGF-beta) is a potential mediator of placental trophoblast functions, including differentiation, hormone production, endometrial invasion, and immunosuppression. Equilibrium binding and affinity-labeling assays were used to investigate the binding characteristics of TGF-beta 1 and TGF-beta 2 on an established human choriocarcinoma trophoblastic cell line (BeWo). The equilibrium binding experiments indicated that the BeWo cells exhibited similar average affinities and total number of binding sites for TGF-beta 1 and TGF-beta 2. The Kd values obtained from Scatchard analyses were approximately 65 pM for 125I-TGF-beta 1 and approximately 40 pM for 125I-TGF-beta 2, with 70,000 and 85,000 sites per cell, respectively. Competitive equilibrium binding experiments indicated that TGF-beta 1 and TGF-beta 2 were equipotent (apparent half maximal inhibition [IC50] approximately 70 pM) and that all binding sites were capable of recognizing both isoforms. Affinity-labeling studies with 125I-TGF-beta 1 and 125I-TGF-beta 2 and the chemical cross-linking agent bis(sulfosuccinimidyl)suberate (BS3) revealed a predominant type III/betaglycan receptor, a low level of apparently heterogeneous type I and II receptors and an additional novel 38-kDa TGF-beta binding glycoprotein that was present both under reducing and nonreducing conditions on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Affinity-labeling saturation and competition studies indicated that the type III/betaglycan component appears to have a 7-fold higher capacity for TGF-beta 1 than for -beta 2 yet exhibits a 5- to 10-fold higher affinity for TGF-beta 2 than for -beta 1. The 38-kDa TGF-beta binding component, an N-linked glycoprotein, exhibits a higher affinity for TGF-beta 2 than for -beta 1 that is strikingly similar to that of the type III/betaglycan receptor. This 38-kDa binding protein appears to be upregulated after methotrexate-induced differentiation of the BeWo cells.
Mol Biol Cell 1992 Nov
PMID:Characterization of transforming growth factor-beta (TGF-beta) receptors on BeWo choriocarcinoma cells including the identification of a novel 38-kDa TGF-beta binding glycoprotein. 133 44

There are at least three isozymes (C alpha, C beta, and C gamma) of the mammalian catalytic (C) subunit of cAMP-dependent protein kinase (PKA) (Beebe, S., Oyen, O., Sandberg, M., Froysa, A., Hansson, V., and Jahnsen, T. (1990) Mol. Endocrinol. 4, 465-475). To compare the C gamma and C alpha isozymes, the respective cDNAs were expressed in permanently transformed Kin-8 PKA-deficient Y1 adrenal cells using the mouse metallothionein promoter. The recombinant C subunits were characterized as immunoreactive, zinc-inducible, cAMP-dependent kinase activities. In contrast to C alpha, histone was a better substrate than Leu-Arg-Arg-Ala-Ser-Leu-Gly (Kemptide) for C gamma. Furthermore, C gamma histone kinase activity was not inhibited by the protein kinase inhibitor peptide (5-24 amide), which has been widely used as a PKA-specific inhibitor. The major C gamma peak (type I) eluted from DEAE-Sepharose at a higher NaCl concentration (120 mM) than the C alpha type I eluted (70 mM). C gamma and C alpha type II eluted between 220 and 240 mM NaCl. C gamma required higher concentrations of cAMP than C alpha did for dissociation from the mutant type I holoenzyme. These differences provided a basis for the separation of the mutant RI-associated isozymes on DEAE-Sepharose. Both C alpha (41-42 kDa) and C gamma (39-40 kDa) were identified by a C subunit antibody after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analysis. Zinc induced the PKA-mediated rounding phenotype in C gamma and C alpha clones, thereby restoring the cells to the parent Y1 adrenal cell phenotype. Collectively, these data indicate that C gamma is an active PKA C subunit but suggest that C gamma and C alpha have different protein and peptide recognition determinants.
 ...
PMID:The C gamma subunit is a unique isozyme of the cAMP-dependent protein kinase. 133 96

We have used myelin basic protein immobilized in sodium dodecyl sulfate-polyacrylamide gels to identify protein kinases after gel electrophoresis, followed by protein kinase reactions. This technique has permitted us to detect three protein kinases in serum-deprived cells transformed by p60src. On induction of cellular transformation by a temperature-sensitive v-src, a p87 protein kinase is activated within 30 min and remains activated in fully transformed cells. The p63 protein kinase is not fully activated until 24 h but remains activated in transformed cells. The commonly studied p42MBPK is rapidly activated within 30 min, and its kinase activity decreases significantly by 24 h, when the p63 enzyme is fully activated. The p42MBPK, as well as the p63 and p87 enzymes, are stimulated by transforming p60c-src mutants but not normal c-src or nonmyristylated p60c-src. In addition, the kinase activity of p63 enzyme, but not of p42MBPK, can be induced in okadaic acid-treated chicken embryo fibroblasts, indicating that phosphatase 2A and/or phosphatase 1 may be involved in the regulation of its activity. Additional data indicate that either p42MBPK or p63 activity correlates with the stimulation of the protein kinase p90RSK. Thus, there may be two independent pathways leading to the activation of the RSK gene product.
Mol Biol Cell 1992 Dec
PMID:Activation of protein serine/threonine kinases p42, p63, and p87 in Rous sarcoma virus-transformed cells: signal transduction/transformation-dependent MBP kinases. 133 88

A simple method for detection of DNA-binding proteins is offered. These proteins can be revealed, following their electrophoretic separation in sodium dodecyl sulfate (SDS)-polyacrylamide gel containing labeled DNA, by washing the gel in buffer to remove SDS and to allow protein renaturation. Protein-free DNA is washed out, remaining in the DNA-binding proteins that restored their original characteristic. After autoradiography these proteins are seen as black bands (by one-dimensional gel electrophoresis) or spots (by two-dimensional gel electrophoresis) on a grey background. High sensitivity of the method is shown by using protein fractions of rat liver and a standard method.
Mol Biol (Mosk)
PMID:[Detection of DNA-binding proteins in polyacrylamide gel after denaturing electrophoresis]. 133 51

In cultured, undifferentiated normal human bronchial epithelial (HBE) cells, transglutaminase activity was localized predominantly in the cytosolic fraction of cell lysates. Upon squamous differentiation, this cytosolic activity declined and was replaced by a 40-fold increase in the activity of particulate (membrane-associated) transglutaminase. Immunoblot analysis demonstrated that the cytosolic transglutaminase was Type II (tissue) transglutaminase and that squamous differentiation shifted gene expression to the Type I (epidermal) transglutaminase. Retinoic acid, an inhibitor of squamous cell differentiation, suppressed the increase in Type I transglutaminase. The decrease in Type II transglutaminase activity was unaffected by retinoic acid. Transforming growth factor-beta 1 (TGF-beta 1) enhanced Type II transglutaminase activity about 10-fold in the undifferentiated cells but did not increase Type I transglutaminase or cholesterol sulfate, two early markers of squamous differentiation. TGF-beta 2 was equivalent to TGF-beta 1 in inducing Type II transglutaminase and in inhibiting the growth of HBE cells. The differentiation-related and TGF-beta-induced changes in transglutaminase activity were reflected in the level of transglutaminase Type I and Type II protein and mRNA. Expression of transglutaminases in lung carcinoma cell lines was variable. No correlation was observed between the expression of Type I transglutaminase and the classification of the cells as squamous cell carcinoma. Several lung carcinoma cell lines exhibited high levels of Type II transglutaminase activity that were increased several-fold by TGF-beta 1 treatment. Retinoic acid was ineffective in altering transglutaminase expression in most cell lines but induced Type II transglutaminase in a time- and dose-dependent manner in NCI-HUT-460 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Jul
PMID:Regulation of type I and type II transglutaminase in normal human bronchial epithelial and lung carcinoma cells. 135 92

The gingival tissues of a male patient suffering from mannosidosis and presenting with gingival overgrowth have been studied. Routine histological assessment highlighted the presence of highly enlarged and vacuolated lymphocytes. The morphology of the connective tissues, fibroblasts and epithelium appeared normal. Immunohistochemical staining of the tissues for chondroitin sulfate proteoglycan demonstrated a normal distribution of this component throughout the connective tissues and intense staining associated with the vacuolated lymphocytes. In vitro studies indicated that fibroblasts isolated from the overgrown tissue did not differ from age and sex matched control fibroblasts with respect to proliferation, protein and proteoglycan synthesis. Taken together, these findings imply that the gingvial overgrowth noted in this patient was not due to a defect in the resident fibroblasts but rather reflected a secondary response to the tissues to impaired host defence mechanisms.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Biochemical and immunohistochemical studies on overgrown gingival tissues associated with mannosidosis. 136 Jul 27


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