Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brown-adipose-tissue mitochondria possess an energy-dissipating ion uniport which is inhibited by purine nucleotides. The regulatory nucleotides bind to a high-affinity site on the outer face of the inner membrane which is independent of the adenine nucleotide translocator. A direct correlation between affinity for the regulatory site and ability to inhibit the ion uniport is demonstrated for a number of nucleotide analogues. 8-Azido-adenosine 5'-triphosphate, a photoaffinity label, also competes with GDP for the binding site and induces respiratory control. 8-Azido-adenosine [gamma-32P]triphosphate was prepared and covalently bound to hamster brown-adipose-tissue mitochondria by near-ultraviolet irradiation. Two major radioactive bands were identified of apparent molecular weight 30000 and 32000, representing 6% and 10% of the inner membrane protein respectively. Selective labelling enabled the 30000-Mr protein to be identified as the carboxyatractylate binding component of the adenine-nucleotide translocator and the 32000-Mr protein to be identified as the regulatory site of the energy-dissipating ion uniport. The levels of the 32000-Mr protein in the inner membrane of guinea-pig brown-adipose-tissue mitochondria correlate with the degree of thermogenic adaptation of the animal.
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PMID:Brown-adipose-tissue mitochondria: photoaffinity labelling of the regulatory site of energy dissipation. 62 84

The human placental receptor (alpha 2MR) for alpha 2-macroglobulin-proteinase complexes contains 3 polypeptides of approx. 500 kDa, 85 kDa, and 40 kDa. N-terminal sequence analysis of the 500 kDa and 85 kDa polypeptides, analysis of a random selection of peptides convering 536 residues from these polypeptides, and analysis of a 1772 bp cDNA encoding part of the 500 kDa polypeptide provide evidence that the 500 kDa and 85 kDa chains are the alpha- and beta-subunits, respectively, of a recently cloned hepatic membrane protein, termed the low density lipoprotein receptor related protein (LRP) (Herz, J., Hamann, U., Rogne, S., Myklebost, O., Gausepohl, H. and Stanley, K.K. (1988) EMBO J. 7, 4119-4127; Herz, J., Kowal, R.C., Goldstein, J.L. and Brown, M.S. (1990) EMBO J. 9, 1769-1776). N-terminal sequence analysis of the 40 kDa polypeptide shows that it is of distinct genetic origin. It is suggested that LRP is the functional receptor for alpha 2-macroglobulin-proteinase complexes (alpha 2MR) and in addition may have as yet unsettled functions in lipoprotein metabolism.
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PMID:Evidence that the newly cloned low-density-lipoprotein receptor related protein (LRP) is the alpha 2-macroglobulin receptor. 170 92

Previous investigations [Jones, Brown, von Glos & Gaunt (1985) Exp. Cell Res. 156, 31-44] have demonstrated the appearance of a new antigenic determinant (recognized by monoclonal antibody 2D6) on the plasma membrane of rat spermatozoa during post-testicular maturation in the epididymis. Identification of the 2D6 antigen on Western blots from one-dimensional SDS/polyacrylamide gels revealed that it co-migrated with a membrane protein (designated Mr 23,000 antigen) present on testicular and immature germ cells, suggesting that one antigen might be a modified version of the other. In the present work, however, we demonstrate that, although they have similar Mr and are present in soluble and membrane-bound forms, the 2D6 and Mr 23,000 antigens are biochemically and immunologically distinct molecules. The properties of the antigens are described and compared. The Mr 23,000 antigen is present on both testicular and cauda epididymidal spermatozoa, has a pI of 6.1, contains no detectable carbohydrate, is not tissue-specific and is degraded by V8 protease. By contrast, the 2D6 antigen is glycosylated, has a broad pI from 4.5 to 6.1, is tissue- and species-specific and is resistant to digestion with V8 protease. Its role in sperm-egg recognition is discussed.
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PMID:Identification and characterization of the 2D6 and Mr 23,000 antigens on the plasma membrane of rat spermatozoa. 243 64

The gene encoding the glycoprotein H (gH) homologue of CMV strain Towne was cloned, sequenced, and expressed. The predicted 742 amino acid gH protein had characteristics typical of a membrane glycoprotein including hydrophobic signal and transmembrane domains and six possible N-linked glycosylation sites. The CMV (Towne) gH gene had a 95% nucleotide identity and a 96.6% amino acid identity with the CMV (AD169) gH gene, as described by M. P. Cranage, G. L. Smith, S. E. Bell, H. Hart, C. Brown, A. T. Bankier, P. Tomlinson, B. G. Barrell, and T. C. Minson (1988, J. Virol. 62, 1416-1422). Transcriptional analysis of the gH gene revealed that the 2.9-kilobase (kb) gH transcript was not detected until late after CMV infection, indicating that the kinetics of gH expression were typical of the late class of CMV genes. The gH gene was expressed in COS cells using a vector in which transcription was driven by the SV40 early promoter. The expression of gH was detected by immunofluorescence using the virus neutralizing murine monoclonal antibody 1G6, which is specific for an 86-kilodalton (kDa) CMV virion membrane protein (p86). Amino acid sequence analysis of p86 tryptic peptides revealed sequence identity with peptides from the deduced gH amino acid sequence, confirming that the gH gene encodes p86. These results indicate that CMV gH can induce virus neutralizing antibodies and establishes gH as a candidate antigen for a subunit vaccine against CMV.
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PMID:The human cytomegalovirus strain Towne glycoprotein H gene encodes glycoprotein p86. 253 98

Insulin-receptor binding and tyrosine kinase activity have been studied in brown adipose tissue from lean and obese mice. Brown adipose tissue carries functional insulin receptors comparable with those of conventional insulin target tissues. The alpha-subunit (Mr, 130,000) was labeled with photoreactive insulin; the beta-subunit (Mr, 95,000) was phosphorylated in a cell-free system, and its level of phosphorylation was increased in a dose-dependent manner by insulin. Two types of obese mice, mice rendered obese by gold thioglucose injection (GTG obese) and genetically obese ob/ob mice, were used. Insulin-receptor number was decreased by 60-70% in obese mice, when expressed per milligram of plasma membrane protein or per microgram of glycoprotein, whereas only a 30-40% diminution was observed in skeletal muscle, indicating that insulin receptors from brown adipose tissue are greatly affected by the downregulation process. Insulin-stimulated autophosphorylation of the insulin-receptor beta-subunit was decreased by 60-70% in preparations of obese mice compared with lean mice in direct proportion to the diminished level of insulin-receptor number. Similarly, the ability of receptors to catalyze the phosphorylation of a synthetic substrate (copolymer glutamate-tyrosine) was reduced. These results suggest that the decrease in insulin-receptor number and in associated tyrosine kinase activity could explain the insulin-resistant glucose uptake and the alteration in diet-induced thermogenesis described in obese animals.
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PMID:Brown adipose tissue in lean and obese mice. Insulin-receptor binding and tyrosine kinase activity. 353 Aug 52

We describe a cell line, designated C100, that displays a 100-fold increase in the major regulatory enzyme of the cholesterol biosynthetic pathway, 3-hydroxy-3-methylglutaryl-coenzyme A reductase [HMG-CoA; mevalonate:NADP(+) oxido-reductase (CoA-acylating), EC 1.1.1.34]. Immunoprecipitation of [(35)S]methionine-labeled enzyme from C100 microsomal membranes prepared in the presence of the protease inhibitors phenyl-methylsulfonyl fluoride and leupeptin revealed two up regulated proteins: a major band of M(r) 92,000 and a minor band of M(r) 63,000. We conclude that the M(r) 92,000 protein is probably the intact form of HMG-CoA reductase protomer based on the following criteria. (i) It is a highly up regulated microsomal membrane protein that coincides with the increase in HMG-CoA reductase specific activity in this cell line. (ii) It is recognized by a specific HMG-CoA reductase antiserum under a variety of stringencies. (iii) Isolation and solubilization of [(35)S]methionine-labeled C100 microsomal membranes in the absence of protease inhibitors resulted in the disappearance of the M(r) 92,000 protein and the appearance of two proteins of M(r) 52,000 and 38,000. (iv) Analysis of cells labeled for 30 min with [(35)S]methionine, well under the half-life of HMG-CoA reductase, revealed only the M(r) 92,000 protein to be present in total cell extract. (v) The previously reported single immunoprecipitation polypeptide for HMG-CoA reductase of M(r) 62,000 [Chin, D. J., Luskey, K. L., Anderson, R. G. W., Faust, J. R., Goldstein, J. L. & Brown, M. S. (1982) Proc. Natl. Acad. Sci. USA 79, 1185-1189] can be isolated and appears to be the result of both proteolysis and sample preparation for NaDodSO(4) gel electrophoresis. Analysis of C100 cells labeled with [(35)S]methionine for 24 hr indicates that the predominant steady-state form of the enzyme is the M(r) 92,000, rather than the M(r) 63,000, protein, further suggesting that the two proteins do not have a classical precursor-product relationship.
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PMID:Overproduction of a Mr 92,000 protomer of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in compactin-resistant C100 cells. 657 13

The retinal pigment epithelium (RPE), like other transport epithelia, has a polarized distribution of membrane and cytoskeletal proteins. The establishment of a polarized phenotype is an essential step in the differentiation of the RPE and the development and maintenance of visual function. Using a monoclonal antibody (MAb 3C4) we have identified a novel membrane protein that is uniquely expressed in chick RPE. We have referred to this protein as REMP for retinal epithelial membrane protein. In these studies we characterized the expression and distribution of this protein during embryonic development and determined its primary structure by cDNA cloning. The developmental expression of REMP was examined by immunocytochemical localization. REMP was first detected in the chick RPE at Embryonic Day 5 (E5) in both apical and basolateral membranes. By E14 the distribution of REMP was restricted to the basolateral surface of the RPE cells. Biochemical fractionation and surface labeling of RPE cells suggested that REMP was an integral protein. The gene encoding REMP was isolated from an E15 chick RPE cDNA library, cloned into lambda gt11, and screened with MAb 3C4. The cDNA was sequenced and found to contain one 1350-bp open reading frame encoding for a 450-amino-acid protein. The deduced amino-acid sequence of REMP shares 32.9% identity with MCT1, a monocarboxylate transporter (Garcia, Goldstein, Pathak, Anderson, and Brown, Cell, 76, 865-873, 1994). By Northern blot analysis, REMP mRNA was detected only in RPE cells. There was an increase in the expression REMP transcript during development but when RPE cells were grown in primary culture the expression of REMP was turned off. The unique expression of REMP in the RPE in vivo would suggest a role for this protein in development and maintenance of normal retinal function.
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PMID:Developmental expression and molecular cloning of REMP, a novel retinal epithelial membrane protein. 762 51

We have examined the process of membrane protein targeting in the polarized cells of the developing Drosophila melanogaster embryo. Human placental alkaline phosphatase (PLAP) is a glycosylphosphatidyl inositol-linked protein that accumulates at the apical membranes of mammalian epithelial cells. A chimeric construct composed of the transmembrane and cytosolic portions of the vesicular stomatitis virus G protein coupled to the ectodomain of PLAP, termed PLAPG, has been found to behave as a basolateral protein (D. A. Brown, B. Crise, and J. K. Rose. Science Wash. DC 232: 34-47, 1989). The subcellular distributions of these proteins were examined in the epithelial and neuronal tissues of transgenic Drosophila embryos. In the surface ectoderm, both PLAP and PLAPG were restricted to the basolateral membranes throughout development. Internal epithelia derived from the surface ectoderm accumulated PLAP at their apical surfaces, whereas PLAPG retained its basolateral distribution. The redistribution of PLAP from the basolateral to the apical plasma membrane was found to be coincident with the invagination of the surface epithelium to form internal structures, suggesting that the sorting pathways that function in the epithelium of the Drosophila embryo are developmentally regulated.
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PMID:Developmental regulation of membrane protein sorting in Drosophila embryos. 763 47

Using expression in Xenopus oocytes, Brown et al. cloned a bovine parathyroid Ca2+ sensing receptor (BoPCaR1). The 1,085 amino acid membrane protein is included in a class of putative seven transmembrane-spanning structures that activate the phosphoinositol pathway through G proteins. Receptor activation presumably elevates intracellular Ca2+ to inhibit secretion of PTH. BoPCaR1 has a big extracellular domain at the amino terminus. BoPCaR1 is most similar to the metabotropic glutamate receptor. BoPCaR1 mRNA is found in cells that have well known Ca2+ sensing function. Inheritance of one inactive Ca2+ sensing receptor gene causes familial hypocalciuric hypercalcemia (FHH) and autosomal dominant hypocalcemia. Mutations in the extracellular domain and in a portion of the third intracellular loop domain decrease the receptor's sensitivity, causing FHH. Extracellular domain mutations increase the receptor's activity at low Ca2+ concentration to cause autosomal familial hypocalcemia.
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PMID:[Parathyroid cells: structure of Ca2+ sensing receptor]. 775 64

We have previously shown that the antiviral protein (AVP) produced by Sindbis virus-infected Aedes albopictus (mosquito) cells (Riedel and Brown, J. Virol. 29, 51-60, 1979) blocks Sindbis viral RNA synthesis and stimulates its own production when applied to uninfected A. albopictus cells (Luo and Brown, Virology 194, 44-49, 1993). From a virus-sensitive (wild-type) mosquito cell line (U4.4) we produced a virus-resistant cell line (L4.4) by exposing U4.4 cells to the AVP. L4.4 cells constitutively produce AVP and fail to replicate viral RNA after infection with virus or transfection with purified viral RNA. In this study we have compared cellular proteins produced as the sensitive cells are temporally converted to the resistant phenotype following exposure to the AVP. A 55-kDa membrane protein associated with lysosomes is found in L4.4 and not in U4.4 cells. This protein is induced during the first 48 hr following treatment of U4.4 cells with the AVP. The correlation of the appearance of the 55-kDa protein with the onset of virus resistance implies that this AVP-induced protein may be responsible for the inhibition of viral RNA replication. Although virus RNA synthesis is blocked in the L4.4 cell line, we have found that the synthesis of nonstructural proteins takes place.
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PMID:A 55-kDa protein induced in Aedes albopictus (mosquito) cells by antiviral protein. 812 21


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