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Query: UNIPROT:P06889 (Mol)
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The emergence of Biotechnology has provided pharmacologists with a variety of methods for investigating the structure, the function, and the regulation of membrane-bound receptors with a precision that was not imagined even five years ago. These new tools have been developed and used to analyze the known catecholamine beta 1- and beta 2-adrenergic receptors and to discover and study a new subtype, the beta 3 receptor. We review here the salient features of each of these three receptors, compare their structural and functional properties, and propose models to explain their differential regulation in time and space. A whole family of proteins has now been found to share with the beta-adrenergic receptors their most prominent features, including seven transmembrane domains and coupling with GTP-binding "G" proteins. We therefore propose that the biotechnology-based procedures developed for the beta-adrenergic receptors will be well applicable to the other members of this "R7G" family of receptors.
Mol Neurobiol
PMID:Biotechnology of beta-adrenergic receptors. 196 19

Exposure of rat heart muscle cells to noradrenaline (1 microM) for 48 hr led to a decrease in the number of beta 1-adrenoceptors of 50% and a concomitant decrease in adenylyl cyclase stimulation by isoprenaline and forskolin of about 60 and 30%, respectively. In addition, the levels of two inhibitory guanine nucleotide-binding protein (Gi protein) alpha-subunits (Gi alpha 40 and Gi alpha 41) were increased in membranes of noradrenaline-treated cells. Evidence is presented that noradrenaline induces this increase by activation of beta-adrenoceptors. First, the noradrenaline action was mimicked by the beta-adrenoceptor agonist isoprenaline. Second, beta-adrenoceptor blockade by timolol but not alpha-adrenoceptor blockade by prazosin prevented the noradrenaline-induced up-regulation of Gi alpha proteins. Furthermore, timolol but not prazosin abolished the noradrenaline-induced down-regulation of beta 1-adrenoceptors and the decreases in receptor-dependent (isoprenaline) and -independent (forskolin) adenylyl cyclase stimulation. The specific protein synthesis inhibitor Pseudomonas exotoxin A was used to study whether the noradrenaline-induced up-regulation of Gi alpha subunits depends on increased synthesis of these proteins. This toxin inhibits peptide chain elongation by ADP-ribosylating elongation factor 2. Treatment of rat heart muscle cells with Pseudomonas exotoxin A (1 ng/ml) completely prevented the noradrenaline-induced increase in Gi alpha proteins, measured by both pertussis toxin-catalyzed ADP-ribosylation and immunoblotting with anti-Gi alpha antibodies. Most importantly, Pseudomonas exotoxin A also completely prevented the noradrenaline-induced decrease in forskolin-stimulated adenylyl cyclase activity. Furthermore, the noradrenaline-induced decrease in isoprenaline-stimulated adenylyl cyclase activity was significantly attenuated by the toxin, although the down-regulation of beta 1-adrenoceptors caused by noradrenaline treatment was not affected. The data presented suggest that prolonged activation of beta-adrenoceptors in rat heart muscle cells, in addition to causing a receptor down-regulation, induces the synthesis of Gi alpha proteins, which then apparently mediate a decreased adenylyl cyclase responsiveness. The data, additionally, suggest that the synthesis of Gi alpha proteins is under control of the activity of the adenylyl cyclase system and that altered levels of these proteins may play a major role in long term regulation of signal transduction by this enzyme.
Mol Pharmacol 1990 May
PMID:Pseudomonas exotoxin A prevents beta-adrenoceptor-induced upregulation of Gi protein alpha-subunits and adenylyl cyclase desensitization in rat heart muscle cells. 197 Oct 89

Thyroid hormone receptors (TR) are ligand-dependent, DNA-binding, trans-acting transcriptional factors belonging to the erbA-related steroid/thyroid hormone receptor superfamily. To better understand the structural and functional characteristics of TRs, we isolated the gene encoding human TR beta 1 (hTR beta 1). The coding region of hTR beta 1 is split into at least eight exons. Each exon well correlates with functional domains of hTR beta 1 protein, and the exon/intron organization is highly conserved when compared with the chicken c-erbA gene which encodes an alpha-type chicken TR. We demonstrate that hTR beta has at least two mRNA forms having different lengths of the 3' untranslated region. We also note several nucleotide corrections of hTR beta 1 cDNA sequence.
Mol Cell Endocrinol 1990 Jun 18
PMID:Structural analysis of human thyroid hormone receptor beta gene. 197 14

The integrin alpha 6 beta 4 is a heterodimer predominantly expressed by epithelia. While no definite receptor function has yet been assigned to it, this integrin may mediate adhesive and/or migratory functions of epithelial cells. We have determined the complete primary structure of both the alpha 6 and beta 4 subunits from cDNA clones isolated from pancreatic carcinoma cell line libraries. The deduced amino acid sequence of alpha 6 is homologous to other integrin alpha chains (18-26% identity). Antibodies to an alpha 6 carboxy terminus peptide immunoprecipitated alpha 6 beta 4 complexes from carcinoma cells and alpha 6 beta 1 complexes from platelets, providing further evidence for the association of alpha 6 with more than one beta subunit. The deduced amino acid sequence of beta 4 predicts an extracellular portion homologous to other integrin beta chains, and a unique cytoplasmic domain comprised of greater than 1,000 residues. This agrees with the structures of the beta 4 cDNAs from normal epithelial cells (Suzuki, S., and Y. Naitoh. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:757-763; Hogervost, F., I. Kuikman, A. E. G. Kr. von dem Borne, and A. Sonnenberg. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:765-770). Compared to these structures, however, the beta 4 cDNAs that we have cloned from carcinoma cells contain extra sequences. One of these is located in the 5'-untranslated region, and may encode regulatory sequences. Another specifies a segment of 70 amino acids in the cytoplasmic tail. Amplification by reverse transcription-polymerase chain reaction of mRNA indicated that multiple forms of beta 4 may exist, possibly due to cell-type specific alternative splicing. The unique structure of beta 4 suggests its involvement in novel cytoskeletal interactions. Consistent with this possibility, alpha 6 beta 4 is mostly concentrated on the basal surface of epithelial cells, but does not colocalize with components of adhesion plaques.
 ...
PMID:Epithelial integrin alpha 6 beta 4: complete primary structure of alpha 6 and variant forms of beta 4. 197 38

In mammalian brain, the activation of GABAA-receptors is associated with the opening of chloride channels, whose function can be allosterically modulated by drugs, in particular by ligands of the benzodiazepine receptor. Agonistic ligands potentiate while inverse agonists reduce the efficiency of GABA. We have cloned cDNAs encoding alpha 1- and beta 1-subunits of the GABAA-receptor from rat brain. When the corresponding RNAs were co-expressed in Xenopus oocytes. GABA-induced currents were recorded which were inhibited by bicuculline and potentiated by pentobarbital. GABA activated the channel in a weakly cooperative manner. Furthermore, the GABA-response was modulated by benzodiazepine receptor ligands. However, not only various agonists but also the antagonist flumazenil and the inverse agonist DMCM potentiated the GABA-response. Thus, alpha 1- and beta 1-subunits are sufficient to form GABAA-receptors which contain benzodiazepine binding sites, although in a functionally restricted form.
Brain Res Mol Brain Res 1990 Aug
PMID:GABAA-receptor expressed from rat brain alpha- and beta-subunit cDNAs displays potentiation by benzodiazepine receptor ligands. 197 69

The electrophysiological effects mediated by beta 2-adrenoceptor stimulation were studied in sheep cardiac Purkinje fibers. beta 2-Adrenoceptor stimulation was achieved by using isoproterenol (ISO) in the presence of the highly selective beta 1-antagonist CGP 20712A. ICI 118,551 was used as a selective beta 2-antagonist. In driven preparations, ISO (0.1 to 1 microM) caused a positive inotropic effect which was associated with the shortening of action potential duration and was completely abolished only by the simultaneous presence of CGP 20712A (0.3 microM) and ICI 118,551 (50 nM). In previously quiescent preparations, ISO (0.1 to 1 microM) induced spontaneous activity in 15 out of 24 preparations. In the presence of CGP 20712A (0.3 microM) only five preparations out of 24 became automatic when exposed to ISO, and their rate of firing was significantly reduced (13 +/- 4 vs. 43 +/- 6 beats/min, P less than 0.05) with respect to ISO alone. CGP 20712A completely abolished the steepening of diastolic depolarization and the increase of the pacemaker current caused by ISO (0.1 to 1 microM). The beta 2-antagonist ICI 118,551 (50 nM) completely failed to modify the effect of ISO on the rate of spontaneous firing, the slope of diastolic depolarization and the pacemaker current. On the other hand, the increase of oscillatory afterpotential (OAP) amplitude caused by ISO in strophanthidin-treated preparations was significantly reduced only by the beta 1-antagonist CGP 20712A, but not by the beta 2-antagonist ICI 118,551. These results demonstrate that beta 2-adrenoceptors are functionally present in sheep Purkinje fibers where their stimulation consistently causes a positive inotropic effect. However, beta 2-adrenoceptors do not appear to affect the processes of normal automaticity, and do not greatly contribute to triggered activity due to OAPs.
J Mol Cell Cardiol 1990 Aug
PMID:Electrophysiological characterization of cardiac beta 2-adrenoceptors in sheep Purkinje fibers. 197 22

Transforming growth factor beta 1 (TGF beta 1) is a potent inhibitor of epithelial cell proliferation. We present data which indicate that epithelial cell proliferation is inhibited when TGF beta 1 is added throughout the prereplicative G1 phase. Cultures become reversibly blocked in late G1 at the G1/S-phase boundary. The inhibitory effects of TGF beta 1 on cell growth occur in the presence of the RNA synthesis inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole. Associated with this inhibitory effect is a decrease in the phosphorylation and histone H1 kinase activity of the p34cdc2 protein kinase. These data suggest that TGF beta 1 growth inhibition in epithelial cells involves the regulation of p34cdc2 activity at the G1/S transition.
Mol Cell Biol 1991 Mar
PMID:Transforming growth factor beta 1 inhibition of p34cdc2 phosphorylation and histone H1 kinase activity is associated with G1/S-phase growth arrest. 199 85

Two new allelic exon-2 HLA-DRB sequences have been identified by using universal and also specific DRB primers. They may correspond to a previously unidentified DRB gene (DRB sigma) and define a new supratypic group ("DRw54") which includes DR1, DR"Br", DR2 and DRw10 bearing HLA haplotypes. This is probably the last HLA-DRB gene to be described in the standard DR haplotypes on the bases of the number of TaqI RFLPs obtained. Sequence comparison with their respective DP and DQ sequences shows that DRB sigma is unequivocally placed within the DRB family and also a constructed "neighbouring homology tree" indicates that DRB sigma gene is probably the eldest in the DRB family, thus the first to diverge from the ancestral DRB gene. An hypothetically deduced DRB sigma beta 1 protein domain was found to be quite different from the corresponding DRB1, DRB3, DRB4 and DRB5 products, since residues 40-55 would bear a longer alpha-helical conformation and would also exist a loss of both the extended conformation at residues 50-54 and the alpha-helix at residues 64-71. Thus, the putative DRB sigma protein would be remarkably different to other DRB ones. Also, a DRB sigma partial transcript (exon-2) has been obtained by PCR of cDNA by using specific DRB sigma oligonucleotides, but a specific Northern blot hybridization has not been achieved.
Mol Immunol
PMID:Exon-2 nucleotide sequences, polymorphism and haplotype distribution of a new HLA-DRB gene: HLA-DRB sigma. 206 26

Maize beta-tubulins are encoded by a large multigene family with at least nine members, as determined by Southern blot analysis. Two expressed genes, represented by the beta 1 genomic clone and the beta 2 cDNA clone, were examined in this study. The two genes encode beta-tubulins which show 94% sequence identity at the amino acid level. Maize beta 1 transcript levels were highest in seedling root tip and tissue culture cells, which are both rapidly dividing tissues. No transcripts were detected in non-dividing leaf tissue. In contrast, beta 2 transcripts were present at relatively high levels in tissue culture cells and at lower levels in seedling root tip and leaf tissue. The electrophoretic mobility of the beta 2 polypeptide was examined in relation to the constellation of beta-tubulin polypeptides on two-dimensional gel western blots of a maize pollen total protein extract. No evidence for post-translational modification of the beta-tubulin polypeptides was found in pollen.
Plant Mol Biol 1990 Dec
PMID:The beta-tubulin gene family in Zea mays: two differentially expressed beta-tubulin genes. 210 87

One of the mouse sperm surface binding sites for zona pellucida ligands exhibits galactosyltransferase (GT) enzyme activity. The present study was undertaken to ascertain whether the GT site behaves as a noncatalytic binding site in its physiological capacity, with no glycosylation of zona ligands, or whether glycosylation of zona ligands is an integral part of sperm-zona binding. The effects of Mn2+, the obligatory cation for GT catalysis, on enzyme activity and sperm-zona binding were examined. With uridine-5'-diphosphogalactose (UDPgal) as galactose donor, and N-acetylglucosamine (GlcNAc) as galactose acceptor, increasing concentrations of Mn2+ in the range of 0.1-10 mM increased GT enzyme activity, with half-maximal activation at 0.65 mM Mn2+ (Vmax = 20 pmol/hr/10(6) cells). In the presence of 0-2 mM Mn2+, sperm-zona binding was inhibited in a concentration-dependent manner; 50% inhibition occurred at 1.25 mM Mn2+. At this concentration, GT enzyme activity was at 65% Vmax. To determine the specificity of the GT site for glycoprotein terminal carbohydrate residues, spermatozoa were incubated with, asialo-ovine submaxillary mucin (N-acetylgalactosamine residues), asialo-, -alpha 1-acid glycoprotein (beta 1-4 galactose residues) ovalbumin (Ov; GlcNAc residues), and asialo-agalacto-/alpha 1-acid glycoprotein (AsAgAGP; GlcN-Ac residues). Only Ov and AsAgAGP acted as acceptors for galactose in the enzyme assay and inhibitors in the sperm-zona binding assay. The kinetics of the interaction of AsAgAGP with the GT site were determined: the Km was 3.6 mg/ml, with Vmax of 33 pmol/hr/10(6) cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1990 Apr
PMID:Further characterization of the mouse sperm surface zona-binding site with galactosyltransferase activity. 210 19


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