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

Steroid hormones, regulators of cell differentiation and proliferation, are believed to play a role in carcinogenesis. Glucocorticoid hormones in particular modulate the expression of a number of proteins implicated in this process. We have investigated the effect of dexamethasone on two cell lines derived from a colon carcinoma, which differ by their tumorigenicity. Dexamethasone was found to inhibit growth of both the progressive (PROb) and the regressive clone (REGb). Upon hormonal treatment, glucocorticoid hormones induced fibronectin secretion by the two clones, whereas PROb cells were found to secrete an additional Mr approximately 43,000 protein. The cellular effect of glucocorticoid hormones being mediated through a specific soluble receptor, we have characterized this protein. The progressive cells (PROb) contained more specific glucocorticoid-binding sites (approximately 170,000 sites per cell) than the regressive ones (REGb cells; approximately 100,000 sites per cell). In both clones, the receptor was associated with the Mr approximately 90,000 heat shock protein to yield large complexes (Stokes radius Rs approximately 7.5 nm), which were dissociated to the same extent upon heat- and salt-treatment. The steroid- and DNA-binding unit of the receptor, characterized under denaturing conditions using an anti-receptor monoclonal antibody was found to be more degraded in the progressive cell line.
J Steroid Biochem Mol Biol 1990 Oct
PMID:Glucocorticoid effects and receptors in two rat colon carcinoma cell lines differing by their tumorigenicity. 226 53

The regulation of fibronectin (FN) gene expression by thyroid hormone was studied. Rats were rendered hypothyroid by thyroidectomy, and the administration of T4 or T3 was used to produce rats in various thyroid states. RNA was extracted from fresh liver, kidney, and heart, and FN mRNA was determined by dot blot hybridization with a 32P-labeled rat FN cDNA probe. The specificity of the hybridization was assessed by Northern blot analysis. In liver, thyroidectomy decreased the abundance of FN mRNA by half, and daily administration of physiological doses of T4 or T3 for 5-6 days restored FN mRNA to the control level. The administration of pharmacological doses of thyroid hormones induced a further increase in the abundance of FN mRNA. A significant dose-dependent correlation between serum levels of T4 and the abundance of FN mRNA was observed in liver. A receptor-saturating dose of T3 (200 micrograms) given to thyroidectomized rats produced a significant increase in FN mRNA within 6 h after injection, indicating that expression of the FN gene was induced relatively rapidly. Moreover, a nuclear run-off assay revealed that thyroid hormone induces expression of the FN gene at least in part at a transcriptional level. The amount of FN mRNA was also determined in kidney and heart of the same rats. Although the abundance of FN mRNA changed by thyroidectomy or the administration of thyroid hormone in those organs, the magnitude of changes were slight compared with those observed in liver. These results suggested that a marked and dose-dependent induction of the FN gene by thyroid hormone occurs specifically in liver.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1990 May
PMID:Specific induction of fibronectin gene in rat liver by thyroid hormone. 227 53

The melting of human plasma fibronectin and its proteolytic fragments has been studied by scanning microcalorimetry to reveal co-operative structural domains in the molecule. It has been established that each of the two similar polypeptide chains of fibronectin has at least 12 structural domains, which differ in stability, size and function. Many of the domains in the N-terminal half of the polypeptide chains appear to be composed of two homologous repeat modules that co-operate to form a single co-operative unit. In the intact fibronectin molecule, the C-terminal regions of both chains seem to interact forming a stable co-operative block.
J Mol Biol 1990 Jan 05
PMID:Co-operative domains in fibronectin. 229 66

Vascular basement membrane contains laminin, fibronectin, proteoglycan and collagens. These molecules have been identified in various tissues by immunolabeling methods and biochemical analyses. We have previously localized laminin, fibronectin and type IV collagen to the basement membrane of rat retinal vessels at the ultrastructural level using an immunoperoxidase method. In this study, we use an immunogold method to re-examine the distribution of these molecules and also to study the localization of heparan sulfate proteoglycan and types I, III and V collagen in the retinal capillary basement membrane. Gold labeling for laminin, type IV collagen and proteoglycan were found diffusely on the basement membrane of the endothelium and pericyte, while that for fibronectin and type V collagen was spotty and variable and that for types I and III collagen was negligible. The segment of basement membrane between the endothelial cell and pericyte appeared less reactive to anti-laminin and anti-type IV collagen than the membrane between the pericyte and perivascular neuroretina. The immunogold method may be useful in quantitative studies of thickened basement membranes under abnormal conditions.
Cell Mol Biol 1990
PMID:Immunogold localization of basement membrane molecules in rat retinal capillaries. 233 11

A synthetic peptide corresponding to amino acid residues 47-63 of human C-reactive protein (CRP) was synthesized and evaluated for its ability to bind phosphorylcholine (PC) and to react with mAb specific for the PC-binding region of CRP. The PC-binding peptide displayed Ca2(+)-independent binding specific for PC and was able to compete against CRP for PC in the presence of Ca2+ ions. The synthetic peptide, like CRP, binds to the extracellular matrix protein fibronectin and the basement membrane protein laminin. The PC-binding peptide was recognized by those mAb generated against the intact CRP molecule that bind at, or near, the functional PC-binding region. In addition, several mAb to the T-15 idiotype present on mouse antibodies specific for PC, recognize an epitope(s) on the PC-binding peptide. Therefore, the 17 amino acid synthetic peptide shares both functional binding activity and antigenicity with the corresponding functional region within the CRP molecule.
Mol Immunol 1990 Jul
PMID:Binding and immunological properties of a synthetic peptide corresponding to the phosphorylcholine-binding region of C-reactive protein. 239 39

Concanavalin A (Con A), a tetravalent lectin, was shown to impair 8 chick embryo fibroblast (8 d CEF) spreading on a laminin (LM) substrate but not on a fibronectin substrate (FN), suggesting that cell surface Con A binding proteins could be involved in 8 d CEF spreading on a LM substrate. The interaction of Con A-binding proteins with Con A is dependent upon the carbohydrate moieties of the isolated glycoproteins; since they interact strongly with Con A-Sepharose and are eluted with 0.3 Mol/l alpha-methylmannopyranoside, the isolated Con A binding-proteins inhibit 8 d CEF adhesion to a Con A substrate to the same extent as alpha-methylmannopyranoside. Furthermore, the isolated Con A binding proteins specifically inhibit in a dose-dependent manner 8 d CEF spreading on LM but not on FN.
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PMID:Cell spreading on laminin substrate involves Con A-binding proteins. 239 33

Fibronectin (Fn), a high molecular weight glycoprotein, was found to constitute 0.43% of the normal adult beagle dog lung. The tissue Fn (TFn) was solubilized by sequential chemical extractions and quantified by ELISA (enzyme-linked immunoabsorbent assay). Subsequent plasmin digestion did not appear to solubilize significantly more Fn. Since 70% of the lung tissue was solubilized by the extractions and plasmin digestions, the TFn quantified represented the bulk of lung Fn. The TFn was identical to plasma fibronectin in the ELISA and one can infer that the Fn molecule is not significantly altered as it is incorporated into the lung connective tissue matrix. Lungs from beagles in which fibrosis had been induced with bleomycin contained 0.99% Fn, more than a twofold increase over normal. In the ELISA TFn from fibrotic lungs gave an inhibition curve of the same shape as did TFn from normal lungs. Thus, Fn from fibrotic lungs is not different qualitatively from Fn from normal lungs in any way detectable with this antiserum. The TFn content of plasmin digests of intact lung was less than that of extracts, which was the converse of results obtained on placenta (B. A. Bray (1985) Biochem. J. 226, 811-815). This difference between lung TFn and placental TFn may be due to differences in degree of glycosylation, which determines susceptibility to proteases.
Exp Mol Pathol 1986 Jun
PMID:The fibronectin content of canine lungs is increased in bleomycin-induced fibrosis. 242 83

To investigate our earlier hypothesis that carbohydrates play a regulatory role in the intracellular transport of secretory glycoproteins, we used 1-deoxynojirimycin (DNJ), and inhibitor of glucosidase I and II of the rough endoplasmic reticulum (RER), to modify the structure of N-linked glycan moieties of secretory glycoproteins of human hepatoma (Hep G2) cells in culture. Using a pulse-chase protocol, we found that treatment of Hep G2 cultures with 1.25 mM DNJ markedly reduced the rate of secretion of alpha 1-protease inhibitor, ceruloplasmin, and alpha 2-macroglobulin, but had no effect on the export of fibronectin, alpha-fetoprotein and transferrin, nor on albumin which lacks carbohydrate. For example, 50% of newly synthesized alpha 1-protease inhibitor, the glycoprotein most dramatically affected, was secreted by 27 min in control cultures versus 110 min in DNJ-treated cultures. Percoll gradient cell fractionation analyses revealed that DNJ inhibited transport of the affected secretory glycoproteins in the RER segment of the ER/Golgi pathway. For example, 50% of newly synthesized alpha 1-protease inhibitor was lost from the RER fraction by 10 min in untreated cells, but 70 min was required for the transport of a similar amount of protein in DNJ-treated cells. DNJ treatment also inhibited the rate at which the N-linked glycan moieties of the affected glycoproteins became resistant to endo H in the Golgi. Since the glycan moiety of secreted forms of the affected glycoproteins were fully processed to the complex structure, suggesting escape from DNJ inhibition, we concluded that removal of terminal glucose residues from the glycan chain of secretory glycoproteins is required for their transport from the RER to the Golgi. We suggest that the oligosaccharide moieties on alpha 1-protease inhibitor, ceruloplasmin and alpha 2-macroglobulin form part of the binding site for a receptor which regulates transport of these glycoproteins.
Mol Cell Biochem
PMID:Differential effects of 1-deoxynojirimycin on the intracellular transport of secretory glycoproteins of human hepatoma cells in culture. 243 31

A monoclonal antibody (MAb 30B6) was recently described by Rogalski and Singer (J. Cell Biol. 101:785-801, 1985) which identified an integral membrane glycoprotein of chicken cells that was associated with a wide variety of sites of actin microfilament attachments to membranes. In this report, we present a further characterization of this integral protein. An immunochemical comparison was made of MAb 30B6 binding properties with those of two other MAbs, JG9 and JG22, which identify a component of a membrane protein complex that interacts with extracellular matrix proteins including fibronectin. We showed that the 110-kilodalton protein recognized by MAb 30B6 in extracts of chicken gizzard smooth muscle is identical, or closely related, to the protein that reacts with MAbs JG9 and JG22. These 110-kilodalton proteins are also structurally closely similar, if not identical, to one another as demonstrated by 125I-tryptic peptide maps. However, competition experiments showed that MAb 30B6 recognizes a different epitope from those recognized by MAbs JG9 and JG22. In addition, the 30B6 antigen is part of a complex that can be isolated on fibronectin columns. These results together establish that the 30B6 antigen is the same as, or closely similar to, the beta-chain of the protein complex named integrin, which is the complex on chicken fibroblast membranes that binds fibronectin. Although the 30B6 antigen is present in a wide range of tissues, its apparent molecular weight on gels varies in different tissues. These differences in apparent molecular weight are due, in large part, to differences in glycosylation.
Mol Cell Biol 1988 Feb
PMID:An integral membrane protein antigen associated with the membrane attachment sites of actin microfilaments is identified as an integrin beta-chain. 245 Nov 20

In order to study human bile duct cells in vitro, cystic ducts were obtained during cholecystectomy and treated with collagenase and mechanical abrasion to isolate biliary epithelial cells. The culture medium was supplemented with 50% of a bovine bile duct conditioned medium obtained by incubating minced bovine extrahepatic bile ducts for 24 hr in Dulbecco's modified Eagle's medium. Cells grew in monolayer and showed contact inhibition at confluency. The epithelial origin of primary cultures was verified by their growth pattern, ultrastructure, and indirect immunofluorescence for cytokeratin. The cultures showed specific immunofluorescence for lysozyme, collagen types I, III, and IV, fibronectin, and laminin, but were negative for collagen type V and factor VIII-associated antigen. Thus, these cultures provide an experimental model for the in vitro study of biliary atresia and other bile duct diseases.
Exp Mol Pathol 1988 Jun
PMID:Characterization of human extrahepatic biliary duct epithelial cells in culture. 245 76


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