Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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We previously reported that there are three different copies of T-cell receptor beta chain constant region (C beta) genes in some rabbits, two of which are present on an approximately 16-kb and one on an approximately 6-kb Eco RI fragment. We also reported that one of the C beta genes on the approximately 16-kb fragment was chimeric, with a 5' cluster of J beta 2 segments and a 3' untranslated region of beta 1 type. Here we report the complete genomic sequences of the D beta 2 and J beta 2 segments associated with the chimeric C beta gene. The rabbit D beta 2 gene segment has very strong similarity to both its human and mouse counterparts. The sequence similarity also extends rather far from the coding region in both 5' and 3' directions. The content and organization of rabbit J beta 2 gene segments is similar to those found in both human and mouse. The rabbit J beta 2 cluster has six functional segments and one pseudogene, as well as a remnant of another pseudogene between J beta 2.2 and J beta 2.3 equivalent to the one found in man in the same location. The J beta 2.5 gene segment of rabbit has lost the splice signal and is a pseudogene unlike its counterparts in man and mouse. Overall analysis of the rabbit D beta 2-J beta 2 region reveals a closer similarity to human than mouse. However, the general organization of the gene segments in the D beta 2-J beta 2 regions of all three species is remarkably conserved over long stretches of DNA sequence.
Mol Immunol 1991 Aug
PMID:Evolutionarily conserved organization and sequences of germline diversity and joining regions of the rabbit T-cell receptor beta 2 chain. 167 59

Rat adipose tissues contain atypical beta receptors that display certain pharmacological sensitivities that are similar to those found in the recently cloned human beta 3 receptor. However, there are also certain pharmacological differences between the human atypical beta 3 receptor and atypical receptors in rodent adipose tissues, which could indicate strong species differences, the existence of multiple atypical receptor subtypes, or both. To help decide among these possibilities, a rat beta 3 receptor clone was obtained and expressed in Chinese hamster ovary cells. The predicted primary structures of the rat and human receptors are greater than 90% similar. Despite this similarity, the pharmacological properties of the rat receptor differed from those reported for the human receptor but were similar to the properties exhibited by atypical receptors in rat adipose tissue. Specifically, the rat beta 3 receptor had a high affinity for BRL 37344 and a relatively low affinity for norepinephrine and was partially activated by the beta 1 and beta 2 receptor antagonist CGP 12177. Northern blot analysis and nuclease protection assays of RNA from rat tissues indicate that the beta 3 receptor is abundantly expressed only in adipose tissues.
Mol Pharmacol 1991 Dec
PMID:Molecular cloning and expression of the rat beta 3-adrenergic receptor. 168 35

Quantitative autoradiography was used to determine the densities of beta 1- and beta 2-adrenoceptors in the atrioventricular conducting system in guinea-pig. (-)[125I]Cyanopindolol (CYP) was used to label beta 1- and beta 2-adrenoceptors in the absence or presence of the beta 1-adrenoceptor selective antagonist CGP 20712A (100 nM) or the beta 2-adrenoceptor selective antagonist ICI 118,551 (70 nM) or the non-selective beta-adrenoceptor antagonist (-)-propranolol (1 microM). Protein in discrete anatomical regions was determined using a densitometric method based on the dye Coomassie brilliant blue G. In the atrioventricular conducting system the proportion of beta 2-adrenoceptors determined by inhibition of total (-)[125I]-CYP binding by CGP 20712A (100 nM) ranged from 32.5% (atrioventricular node) to 48.7% (left bundle branch). In the atrioventricular node (16.8 fmol/mg protein), bundle of His (12.1 fmol/mg protein), right (17.4 fmol/mg protein) and left (21.1 fmol/mg protein) bundle branches and Purkinje cells there was a higher density of beta 2-adrenoceptors than in the interventricular septum (8.4 fmol/mg protein) and right atria (8.3 fmol/mg protein). The medial smooth muscle of the aorta, aortic valve, adventitia of the aorta, nerve tissue, tricuspid and mitral valves contained only beta 2-adrenoceptors. It is speculated that the use of beta-adrenoceptor antagonists to control cardiac arrhythmias involving a defect in conduction in the atrioventricular node should take into consideration both beta 1- and beta 2-adrenoceptors.
J Mol Cell Cardiol 1990 Apr
PMID:Densitometric analysis of beta 1- and beta 2-adrenoceptors in guinea-pig atrioventricular conducting system. 169 96

Several glycosylated macromolecules associated with normal and malignant pancreatic ductal cells have been described. We have generated a monoclonal antibody, LD-B1, by immunizing Balb/c mice with the postmicrosomal extract of fresh human pancreatic ductal carcinoma tissue and used it in this study to characterize the nature of the target antigen. The antigen detected by LD-B1 antibody was purified to homogeneity by affinity chromatography. Enzymatic and biochemical analysis showed it to be a nonsialylated glycoprotein that on Western blotting and immunoprecipitation analyses had an apparent molecular weight of 300-400 kDa. The mobility on gels was not affected by reducing or denaturing conditions. Competitive inhibition assays with various MoAbs and lectins indicated that the epitope recognized by LD-B1 antibody involves the carbohydrate sequence Gal beta 1----3Gal beta 1----3(or 4)GlcNAc beta 1----3Gal. Using a double determinant sandwich ELISA, elevated antigen levels were detected in the sera of 5 of 6 patients with pancreatic carcinoma, 0 of 3 patients with chronic pancreatitis, and 12 of 137 normal controls. These results suggest that patients with pancreatic carcinoma exhibit altered expression of a heavily glycosylated molecule related to a blood group precursor immunodeterminant.
Exp Mol Pathol 1990 Oct
PMID:Biochemical characterization and serological immunoassay of a pancreatic carcinoma-associated antigen defined by monoclonal antibody LD-B1. 170 61

F62 LOS of Neisseria gonorrhoeae consists of two components. The higher molecular weight (MW) component is recognized by monoclonal antibody (MAb) 1-1-M and the smaller MW component by MAb 3F11. Epitope expression of the two LOS components and their partial structures were investigated by treating the F62 LOS with several glycosidases and then monitoring their antigenicity with the two mouse IgM MAbs. The 1-1-M-defined LOS component was cleaved with both beta-N-acetylhexosaminidase and endo-beta-galactosidase, and each cleavage resulted in the loss of expression of the 1-1-M-defined epitope. The N-acetylhexosamine (HexNAc) released by the hexosaminidase was found to be GalNAc, and the smaller oligosaccharide released by the endo enzyme was identified to be a dimer GalNAc beta----Gal. In contrast, the MAb 3F11-defined LOS component was not digested by the endo galactosidase, but it was cleaved with alpha and beta-galactosidase, and expression of the MAb 3F11-defined LOS epitope expression of the MAb 3F11-defined LOS was abolished by the treatment with each of two exo enzymes. MAb 3F11 bound to the 1-1-M-defined LOS component resulting from the removal of the beta-GalNAc residue, and the resulting LOS was further cleaved with beta-galactosidase, but not with alpha-galactosidase. From these results, we conclude the following: (1) MAbs 1-1-M and 3F11 both recognize the non-reducing termini of the LOS components; (2) the 1-1-M-defined LOS component has the GalNAc beta----Gal beta 1----4-Glc (or GlcNAc) structure, and the GalNAc beta----Gal residue is involved in the MAb 1-1-M-defined epitope; (3) the MAb 3F11-defined LOS component may not have a Gal beta 1----4GlcNAc beta 1----4Gal beta 1----4Glc structure within the molecule. However, it has beta-Gal residue at its non-reducing terminus, and this residue is involved in the MAb 3F11-defined epitope; (4) the two LOS components share a similar antigenic structure, and the 3F11-defined epitope structure is present in the MAb 1-1-M-defined LOS component. Expression of this epitope within the 1-1-M-defined LOS molecule is blocked by the beta-GalNAc residue; however, the beta-GalNAc residue at the non-reducing end may be not the only structural difference between the two components.
Mol Immunol 1991 Nov
PMID:Epitope expression and partial structural characterization of F62 lipooligosaccharide (LOS) of Neisseria gonorrhoeae: IgM monoclonal antibodies (3F11 and 1-1-M) recognize non-reducing termini of the LOS components. 172 May 5

Transforming growth factor-beta 1 (TGF beta 1) is a multifunctional regulator of cell growth and differentiation. We report here that TGF beta 1 decreased the proliferation of nontransformed bovine anterior pituitary-derived cells grown in culture. We have previously demonstrated that these cells express both TGF alpha and its receptor [the epidermal growth factor (EGF) receptor] and that expression can be stimulated by phorbol ester (TPA) and EGF. TGF beta 1 treatment over a 2-day period decreased the proliferation of pituitary cells. This decreased growth rate was accompanied by a decrease in the TGF alpha mRNA level. The effect of TGF beta 1 on TGF alpha mRNA down-regulation was both dose dependent (maximal effect observed at 1.0 ng/ml TGF beta 1) and time dependent (minimum of 2-day treatment with TGF beta 1 was required before a decrease in TGF alpha mRNA was observed). Studies on TGF alpha mRNA stability indicated that TGF beta 1 did not alter the TGF alpha mRNA half-life. Treatment of the TGF beta 1 down-regulated cells with EGF resulted in the stimulation of TGF alpha mRNA levels; thus, the TGF beta 1-treated cells remained responsive to EGF. The decreased proliferation in response to TGF beta 1 could be only partially reversed by simultaneous treatment of the cells with EGF (10(-9)M) and TGF beta 1 (3.0 ng/ml). Qualitatively, the TGF beta 1-induced reduction of TGF alpha mRNA content was independent of cell density. TGF beta 1 treatment of the anterior pituitary-derived cells also reduced the levels of c-myc and EGF receptor mRNA. These results represent the first demonstration of the down-regulation of TGF alpha synthesis by a polypeptide growth factor and suggest that TGF beta 1 may be a physiological regulator of TGF alpha production in vivo.
Mol Endocrinol 1991 Oct
PMID:Transforming growth factor-beta (TGF beta) inhibits TGF alpha expression in bovine anterior pituitary-derived cells. 172 43

Polychlorinated hydrocarbons known to be nongenotoxic carcinogens were screened as activators of protein kinase C (PKC)-beta 1 either at high concentrations of Ca2+ or in the absence of Ca2+ (i.e., with 1 mM ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N',-tetraacetic acid). Of those compounds tested, kepone and dicofol significantly stimulated PKC activity in the absence, but not the presence, of Ca2+. PKC activation was most pronounced in the presence of phosphatidylserine. Kepone and dicofol stimulated PKC activity 26% and 13%, respectively, as compared with the PKC activity (100%) stimulated by the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Northern blot analysis of expression of TPA-inducible genes by kepone showed slight expression of phorbin and ornithine decarboxylase in murine embryo fibroblasts. Future studies are required to determine the relevance of PKC activation by kepone and dicofol to the known carcinogenicity of these compounds.
Mol Carcinog 1991
PMID:Two polychlorinated hydrocarbons cause phospholipid-dependent protein kinase C activation in vitro in the absence of calcium. 172 72

We found previously that transforming growth factor-beta 1 (TGF beta 1) mRNA levels are markedly elevated in rat prostate cancer (Dunning R3327 sublines) compared to levels in normal prostate. Our goal was to determine whether elevated expression of TGF beta 1 is biologically relevant to prostate cancer growth in vivo. We chose as our model the R3327-MATLyLu prostate cancer epithelial cell line, which produces metastatic anaplastic tumors when reinoculated in vivo. Our approach was to stably transfect MATLyLu cells with an expression vector that codes for latent TGF beta 1 and to isolate subclones of cells that over-expressed TGF beta 1 mRNA. We also isolated a subclone of MATLyLu cells transfected with a control vector lacking the TGF beta 1 cDNA insert. We then studied the growth of these cells in vivo and in vitro. Twenty days after sc inoculation of 10(6) cells in vivo, TGF beta 1-overproducing MATLyLu tumors were 50% larger, markedly less necrotic, and produced more extensive metastatic disease (lung metastases in 73% of all lobes and lymph node metastases in 88% of animals) compared to control MATLyLu tumors (lung metastases, 21%; lymph node metastases, 7%). Thus, TGF beta 1 produced in vivo is biologically active and can promote prostate cancer growth, viability, and aggressiveness, perhaps via effects on the host and/or on the tumor cells themselves. When followed in vitro, TGF beta 1-overproducing cells became growth inhibited, but this effect was transient as cells subsequently resumed proliferating. Growth inhibition was due to TGF beta, because it could be prevented by TGF beta-neutralizing antibody. Therefore, prostate cancer cells can activate and respond to secreted latent TGF beta 1, and although the cells are transiently inhibited in vitro, there is no net inhibition of growth. The ability of the cells to respond to endogenously produced TGF beta 1 suggests that TGF beta 1 overexpression enhances tumor growth in vivo at least in part via an effect of TGF beta 1 on the tumor cells themselves.
Mol Endocrinol 1992 Jan
PMID:Transforming growth factor-beta 1 overproduction in prostate cancer: effects on growth in vivo and in vitro. 173 67

We have examined the expression of beta-tubulin genes in the parasitic nematode, Brugia pahangi. A genomic library was constructed and screened by hybridization with a Haemonchus contortus beta-tubulin cDNA fragment which recognizes several B. pahangi beta-tubulin sequences, including sequences which correspond to the previously characterized beta 1-tubulin gene. The B. pahangi beta 2-tubulin gene was isolated by selecting clones which hybridize to the H. contortus beta-tubulin gene but which do not hybridize to the beta 1-tubulin gene. A partial sequence of the beta 2-tubulin gene confirms that it codes for a distinct beta-tubulin. Southern hybridization analyses show that the beta 2-tubulin sequence exists as a single copy gene within the B. pahangi genome. Expression of the beta 2-tubulin gene is developmentally regulated and the message is found predominantly in adult male worms, whereas the beta 1-tubulin gene is expressed in microfilariae and approximately equal levels of the transcript are found in male and female adult worms. During mRNA maturation the beta 1-tubulin mRNA of microfilariae and adult worms acquires a trans-spliced leader identical to the SL1 of Caenorhabditis elegans.
Mol Biochem Parasitol 1992 Feb
PMID:Identification of a novel Brugia pahangi beta-tubulin gene (beta 2) and a 22-nucleotide spliced leader sequence on beta 1-tubulin mRNA. 174 Oct 15

The three factor crosses between the donor strain Bacillus subtilis 168 harbouring the plasmid pUB102-4, Bacillus thuringiensis strain carrying the mobilizing plasmid pAM beta 1 and recipient strain Lactobacillus fermenti were conducted in order to elaborate the optimal conditions of the plasmid pUB102-4 mobilization for transfer into gram-positive microorganisms and to elucidate the possible expression of endogluconase genes in a lactobacillus strain. The Lactobacillus fermenti transconjugants carrying the pUB102-4 plasmid were obtained in the three factor reciprocal crosses with the streptococcus recipient strain and Bacillus subtilis recipients. The presence of the plasmids in transconjugants was confirmed by colony hybridization with the [32P]-labelled plasmid DNA and KMC-ase activity in transconjugant cells. The proposed system of crosses using the high copy number plasmid derivatives of pUB110 mobilized with high frequency by the pAM beta 1 plasmid demonstrates the possibility to increase the circle of gram-positive host bacteria avoiding time and labour consuming operations.
Mol Gen Mikrobiol Virusol 1991 Sep
PMID:[Mobilization transfer of the pUB110 plasmid between gram-positive bacteria]. 174 69


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