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)

The ratio of mRNA not selected for polyadenylation (non-poly(A)+ selected) to mRNA selected for polyadenylation (poly(A)+) for the beta 1, alpha 1 and gamma 2 subunits of the GABAA receptor complex was examined in rats as a function of age. RNA was extracted from whole brain of rats that were either 0, 1, 3, 5 or over 60 days of postnatal age. Poly(A)+ mRNA was purified by oligo(dT)-cellulose chromatography. Non-poly(A)+ selected mRNA and poly(A)+ mRNA for the GABAA receptor beta 1, alpha 1 and gamma 2 subunits were examined by Northern blot analysis using cDNA probes specific for these subunits. Levels of GABAA receptor beta 1 subunit mRNA were also examined by solution hybridization analysis with a beta 1 riboprobe. Analysis of Northern blots revealed that levels of poly(A)+ beta 1 subunit mRNA were highest at 0 days of age, but decreased and reached adult levels by 5 days of postnatal age. However, levels of the beta 1 subunit message extracted from non-poly(A)+ selected mRNA were not significantly different at any of the ages examined, suggesting the existence of a population of beta 1 subunit mRNA that is not polyadenylated. The age-related discrepancy between beta 1 subunit levels measured in non-poly(A)+ selected mRNA and poly(A)+ mRNA was also observed using solution hybridization analysis. In contrast, levels of both non-poly(A)+ selected mRNA and poly(A)+ mRNA for the alpha 1 subunit of the GABAA complex increased from 0 days of age to adulthood. Similarly, levels of both non-poly(A)+ selected mRNA and poly(A)+ mRNA for the GABAA receptor gamma 2 subunit increased with age.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1992 Jul
PMID:Developmental profile of polyadenylated and non-polyadenylated GABAA receptor subunit mRNAs. 127 41

A 1.45 kb DNA sequence encoding the rat alpha 6 GABAA receptor subunit (nucleotides 33-1483) was cloned from a Sprague-Dawley rat brain cDNA library by PCR amplification. Dideoxy sequencing of two individual clones revealed that the nucleotide sequence differed at only one basepair (T480-->G) from that published previously. This difference altered the deduced amino acid sequence, producing a conservative amino acid substitution (His121-->Gln). A Gln residue is present at the same location in the bovine alpha 6 subunit. Restriction endonuclease analysis of the total PCR product demonstrated that this variant of the rat alpha 6 subunit was the only allele found in this particular rat brain library, the original allele was not present. These results were further verified by RNAse protection assays performed with RNA isolated from individual rat cerebella. alpha 6, beta 1, and gamma 2S subunits were transiently expressed in L929 cells for electrophysiological analysis. Whole-cell recordings obtained from the cells demonstrated that GABAA receptor channels with the expected GABA and benzodiazepine pharmacology were produced. Excised outside out single channel recordings from the same cells revealed that GABA elicited brief duration openings to a 33 pS main conductance level and to at least one smaller (approximately 21 pS) subconductance level. Thus this allelic variant of rat alpha 6 subunit could assemble with other subunits to form a functional GABAA receptor channel with similar properties to the original allelic form.
Brain Res Mol Brain Res 1992 Nov
PMID:Molecular and electrophysiological characterization of a allelic variant of the rat alpha 6 GABAA receptor subunit. 128 Dec 55

Transforming growth factor-beta (TGF beta) has been implicated in the regulation of hepatocyte function. We have examined TGF beta 1 regulation of albumin and alpha-fetoprotein (AFP) mRNA levels in a well differentiated mouse hepatoma cell line (BWTG3). TGF beta 1 reversibly decreased steady state mRNA levels of both albumin and AFP. By nuclear run-on assays, we found that TGF beta 1 caused no significant change in transcription rates for albumin or AFP. Pretreatment with actinomycin-D prevented the TGF beta 1-induced decrease in albumin and AFP mRNA levels. Also, if cells were treated with actinomycin-D after a 12-h exposure to TGF beta 1, actinomycin-D abrogated the further decrease in albumin and AFP mRNA levels that occurred after treatment with TGF beta 1 alone. Cycloheximide pretreatment blocked the TGF beta 1-induced decrease in albumin and AFP mRNA levels. TGF beta 1 altered neither the rate of BWTG3 cell growth nor the levels of mRNA for the growth-associated protooncogene c-myc. These data suggest that TGF beta 1 has regulatory effects on specific hepatocyte functions that are independent of growth regulatory effects. The decrease in albumin and AFP mRNAs caused by TGF beta 1 is posttranscriptional and dependent upon de novo RNA and protein synthesis.
Mol Endocrinol 1992 Nov
PMID:Posttranscriptional regulation of albumin and alpha-fetoprotein messenger RNA by transforming growth factor-beta 1 requires de novo RNA and protein synthesis. 128 69

Although tissue-specific expression of the alpha 1 and beta 1 thyroid hormone receptors (TR-alpha 1 and TR-beta 1) suggests isoform-specific function, transfection studies to date have failed to show consistent differences in their ability to regulate gene expression. We here provide evidence that TR-beta 1 but not TR-alpha 1 regulates the expression of the gene coding for PCP-2 in cerebellar Purkinje cells during neonatal rat development and that such regulation appears to be both T3 dependent and T3 independent. Examination of neonatal rats revealed that the levels of three mRNAs expressed in cerebellar Purkinje cells (myoinositol-1,4,5-triphosphate receptor, calbindin, and PCP-2) rise from neonatal day 1 to day 15. This rise is preceded by the previously documented surge in brain T3 and TR-beta 1. Methimazole-induced hypothyroidism sharply reduces, but does not abolish, the rise in these mRNAs. Concomitant T3 administration normalizes the process. In order to establish more directly the role of TR-beta 1 and T3, cotransfection experiments were performed in CHO cells with PCP-2-lacZ construct and TR isoforms. These studies showed that TR-beta 1, even in the absence of T3, regulated the expression of the transfected PCP-2 construct. T3 augments the response to TR-beta 1 alone by 40% (P < .01). TR-alpha 1 had no effect on PCP-2-lacZ expression either in the presence or absence of T3.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1992 Nov
PMID:Beta 1 isoform-specific regulation of a triiodothyronine-induced gene during cerebellar development. 128 72

Polyclonal (RP) and monoclonal (Ab) antibodies were raised against synthetic peptides (or fusion proteins) corresponding to amino acid sequences unique to human and mouse retinoic acid receptor-beta (RAR beta) isoforms. Antibodies directed against the A2 region [Ab6 beta 2(A2), Ab7 beta 2(A2), and RP beta 2(A2)], the D2 region [RP beta(D2)], or the F region [Ab8 beta(F)2, RP beta(F)1, and RP beta(F)2] were selected. The monoclonal and polyclonal antibodies directed against the D2 and F regions specifically immunoprecipitated and recognized by Western blotting all human and mouse RAR beta isoforms (mRAR beta 1, -beta 2, -beta 3, and -beta 4), produced in COS-1 cells transfected with expression vectors containing the corresponding RAR beta cDNA. Furthermore, in gel retardation assays, the monoclonal antibodies supershifted RAR beta protein-RA response element oligonucleotide complexes. Antibodies directed against the A2 region were specific for the RAR beta 2 isoform. The above antibodies allowed us to detect the presence of mRAR beta 2 proteins in mouse embryos and to show that their presence in embryonal carcinoma cells (F9 and P19 cell lines) is dependent upon RA treatment. The antibodies were also used to demonstrate that RAR beta proteins produced by transfection in COS-1 cells are phosphorylated. RAR beta 2 phosphorylation was not affected by RA treatment, whereas the phosphorylation of RAR beta 1 and RAR beta 3 isoforms was greatly enhanced by RA. We also show that, in contrast to RAR alpha 1 and RAR gamma 1, RAR beta 2 proteins contain phosphotyrosine residues and are only weakly phosphorylated in vitro by cAMP-dependent protein kinase. These results support our previous proposal that the various receptors have distinct functions in the RA-signaling pathway.
Mol Endocrinol 1992 Dec
PMID:Retinoic acid receptor-beta: immunodetection and phosphorylation on tyrosine residues. 128 41

Cell growth and tumor transformation can be restrained in certain cell systems by the action of transforming growth factor beta (TGF-beta). It has been established that the mechanism whereby TGF-beta 1 inhibits cell growth does not interfere with the triggering of early mitogenic signal transduction mechanisms. Phospholipase C-catalyzed hydrolysis of phosphatidylcholine (PC) is a relatively late step in the cascade activated by growth factors. Therefore, conceivably activation of phospholipase C-catalyzed hydrolysis of PC could be the target of TGF-beta 1 action. In the study reported here, we demonstrate that TGF-beta 1 inhibits the coupling of ras p21 to the activation of PC hydrolysis, which appears to be critical for the antiproliferative effects of TGF-beta 1.
Mol Cell Biol 1992 Jan
PMID:Phospholipase C-mediated hydrolysis of phosphatidylcholine is a target of transforming growth factor beta 1 inhibitory signals. 130 92

The GABAA receptor belongs to the ligand-gated ion channel receptor superfamily and appears to be composed of from 4 to 5 subunits which interact with each other. Molecular cloning of cDNAs encoding the different subunits of the GABAA receptor has revealed an unexpected heterogeneity which includes at least 4 homologous classes of subunits: these classes, designated as alpha, beta, gamma, and delta contain multiple variants. We have measured the steady-state levels of mRNAs encoding different (alpha 1, alpha 4, beta 1, beta 2, beta 3, gamma 2 long, gamma 2 short and delta) GABAA receptor subunits in the rat anterior pituitary and cerebellum using a polymerase chain reaction (PCR)-derived method. We found that pituitary cells express mRNAs encoding the alpha 1, beta 1 and beta 3 GABAA receptor subunits whereas the transcripts for alpha 4, beta 2 and delta were undetectable. We also found that pituitary cells selectively express the short isoform of the gamma 2 subunit mRNA. These data indicate that the expression of the various GABAA receptor subunits is cell-specific and support the concept that the diversity in function and pharmacology of the GABAA receptor is based on the ability of cells to specify the expression of selective GABAA receptor subunits.
Brain Res Mol Brain Res 1992 Mar
PMID:Rat pituitary cells selectively express mRNA encoding the short isoform of the y2 GABAA receptor subunit. 131 11

Transforming growth factor beta 1 (TGF beta 1) mRNA expression was examined after hypoxia-ischemia in rat brains using in situ hybridization. Twenty-one-day-old Wistar rats had unilateral ligation of the right carotid artery followed by either 15 or 90 min inhalational hypoxia. Fifteen min of hypoxia resulted in moderate damage with selective neuronal loss in cortical layer 3 and in the hippocampus of the ligated hemisphere. Seventy-two hours after hypoxia TGF beta 1 expression was markedly increased above control levels in those sites. Levels were normal after 120 h. Ninety min of hypoxia led to an infarction of the lateral cerebral cortex and hippocampus of the ligated hemisphere. One hour after hypoxia TGF beta 1 mRNA was expressed in the hippocampus of the damaged side. Seventy-two and 120 h after hypoxia, expressing cells were found throughout the cerebral cortex, piriform cortex, striatum, thalamus and hippocampus of the infarcted side. These data show that TGF beta 1 mRNA expression is induced after a hypoxic-ischemic insult in the brain. TGF beta 1 may be involved in post-asphyxial repair mechanisms.
Brain Res Mol Brain Res 1992 Mar
PMID:Hypoxia-ischemia induces transforming growth factor beta 1 mRNA in the infant rat brain. 131 21

The extracellular matrix has been shown to influence the differentiation of epithelial cells. To identify cues from the extracellular matrix controlling the differentiation of tracheal gland serous cells, we examined the effects of culturing these cells on various extracellular matrix proteins. Bovine tracheal gland (BTG) serous cells attached to Type IV collagen (COL IV), laminin (LM), and fibronectin (FN) in a concentration-dependent manner. Morphologic analysis showed that cells formed confluent monolayers on COL IV or LM, whereas on FN, cells formed birefringent spheres. Metabolic labeling experiments showed that [35S]methionine-labeled protein bands at 68, 105, and 120 kD were prominent when cells were grown on COL IV or LM, but were lost or reduced when the cells were grown on FN. COL IV also enhanced the expression of proteins at 14, 16.5, 18, and 21.5 kD. Attachment to all substrates was inhibited by an antibody directed against beta 1 integrins. This antibody precipitated several integrin heterodimers from a BTG cell membrane extract, caused partial retraction of cells from all substrates, and strongly suppressed the expression of COL IV- and LM-dependent proteins. Control experiments indicated that the latter did not require conspicuous changes in cell shape. These results show that some biochemical properties of serous cells are regulated by integrin-mediated effects of extracellular matrix proteins in vitro and suggest that similar regulation may occur during normal development and remodeling of the glands in vivo.
Am J Respir Cell Mol Biol 1992 May
PMID:Extracellular matrix proteins regulate morphologic and biochemical properties of tracheal gland serous cells through integrins. 131 31

Regulation of multiple c-erbA gene expression was studied in rat thyroid FRTL-5 cells. Two species of erbA alpha (alpha 1 and alpha 2) mRNA and one species of erbA beta (beta 1) mRNA were identified by Northern blot analysis. Withdrawal of thyrotropin (TSH), insulin and serum from the complete medium resulted in an increase in alpha 1 and alpha 2 erbA mRNA levels without altering the level of erbA beta 1 mRNA. Readdition of TSH, N6,2'-O-dibutyryl cAMP or forskolin caused a transient reduction of alpha 1 and alpha 2 mRNA levels (75-90%) at 3-12 h. The alpha 1 and alpha 2 mRNA levels were restored at 24 h. The TSH action was dose-dependent showing the half-maximal effect at around 10(-9) M. Readdition of TSH did not show any effect on beta 1 mRNA level. The action of TSH was not dependent on ongoing protein synthesis but required ongoing transcription. Inhibitors of thyroid hormone biosynthesis, propylthiouracil and methylmercaptoimidazole, did not show any effect on TSH action. Readdition of insulin or insulin-like growth factor I (IGF-I) caused a dose-dependent reduction of alpha 1 and alpha 2 mRNA levels without any effect on beta 1 mRNA level. Their action was slower than TSH and persistent. The actions of insulin and IGF-I were dependent on both ongoing translation and transcription. These results indicate that TSH and insulin/IGF-I reduce levels of c-erbA alpha 1 and alpha 2 mRNA possibly by two distinct mechanisms without altering c-erbA beta 1 mRNA level in FRTL-5 cells.
Mol Cell Endocrinol 1992 Apr
PMID:Differential regulation of multiple c-erbA expression by thyrotropin, insulin and insulin-like growth factor I in rat thyroid FRTL-5 cells. 131 55


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