UNIPROT:P67775 - FACTA Search

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Query: UNIPROT:P67775 (alpha isoform)
797 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A characteristic feature of the obligatory control of amphibian metamorphosis by thyroid hormones is the early acquisition of response of tadpole tissues to these hormones well before the latter are secreted, with 'exponentially' increasing hormonal sensitivity upon the onset of metamorphosis. We have therefore analyzed the expression of the two thyroid hormone receptor genes (TR alpha and beta) before, during and after metamorphosis in Xenopus tadpoles and froglets. Using non-cross-hybridizing cRNA probes for 5' and 3' sequences of Xenopus TR alpha and beta transcripts for RNAase protection assays, the two mRNAs can be detected in tadpoles as early as stage 39. Their concentration increases abruptly at stage 44 and continues to increase differentially at the onset of metamorphosis (stage 55) and through metamorphic climax at stages 58-62, after which they decline upon completion of metamorphosis at stage 66. Quantitative densitometric scanning of autoradiograms showed that, although the concentration of TR beta transcripts is about 1/30th of that of TR alpha mRNA at stages 44-48, depending on the region, it accumulates 3-10 times more rapidly than does the alpha isoform during further development. A substantial proportion of the increase in TR beta mRNA is localized to the head region of tadpoles. Using the hormone-binding domain (HBD) and 3' end of Xenopus TR alpha cRNA as probe for in situ hybridization, the highest concentration of TR transcripts in stage 44 tadpoles is seen in the brain and spinal cord. High concentrations of mRNA are also present in the intestinal epithelium and tail tip, tissues programmed for regression. At later stages (55 onwards), strong hybridization signals are also exhibited by hindlimb buds. This pattern persists through metamorphic climax, after which TR mRNAs decline in all tissues to low levels in froglets at stage 66. In developing froglets, TR transcripts were detected in large amounts in the cytoplasm of stage 1 and 2 oocytes but the rate of their accumulation did not increase with further oocyte growth. This observation raises the possibility that the response to thyroid hormones at early stages of tadpoles (42-44) may be due to TR synthesized on maternally derived mRNA. Exposure of tadpoles at premetamorphic stages (48-52) to exogenous thyroid hormone (T3) substantially enhanced the accumulation of TR mRNA, especially that of TR beta message, which could explain the accelerated increase in sensitivity of tadpoles to thyroid hormones at the onset of natural metamorphosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Developmental and regional expression of thyroid hormone receptor genes during Xenopus metamorphosis. 193 2

Thyroid hormone receptors (TRs) are nuclear proteins that regulate gene expression through interactions with specific DNA sequences. It is well known that thyroid hormones have critical functions in the control of normal brain development. In the rat brain, at least three mRNA species are generated by differential processing of the TR alpha transcript. Only one of the isoforms, TR alpha-1, is a transcriptional activator, while the regulatory roles of the carboxy-terminal variants TR alpha-2 and TR alpha-2v remain unclear. In this study we have used polymerase chain reaction amplification of total RNA to compare TR alpha-1, TR alpha-2, and TR alpha-2v mRNA levels in the brainstem, cerebellum, cerebrum, midbrain, and olfactory bulbs of developing neonatal brains in rats. RNA was collected 5, 10, 15, 20, and 25 days after birth from both normal and hypothyroid animals. Coordinate expression of all three isoforms was observed in most tissues during development, with TR alpha-2 generally maintaining the highest level of expression, and TR alpha-1 the lowest. In hypothyroid tissues, TR alpha-1 message was generally increased, while TR alpha-2 was not. To explore the possible roles of the TR alpha isoforms, we have compared their DNA-binding activities. We report that compared to TR alpha-1, the carboxy-terminal variants TR alpha-2 and TR alpha-2v show different binding patterns with a thyroid hormone response element, suggesting that they bind only poorly as monomers. The varying ratios of the TR alpha isoform expression together with their distinct binding patterns and reported repressor functions suggest that TR alpha isoforms have important roles during brain development and function, and may serve to fine-tune the biological responses to thyroid hormone.
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PMID:Coordinate expression of functionally distinct thyroid hormone receptor alpha isoforms during neonatal brain development. 194 7

We have investigated the time course of expression of the alpha and beta triad junctional foot proteins in embryonic chick pectoral muscle. The level of [3H]ryanodine binding in muscle homogenates is low until day E20 of embryonic development, then increases dramatically at the time of hatching reaching adult levels by day N7 posthatch. The alpha and beta foot protein isoforms increase in abundance concomitantly with [3H]ryanodine binding. Using foot protein isoform-specific antibodies, the alpha foot protein is detected in a majority of fibers in day E10 muscle, while the beta isoform is first observed at low levels in a few fibers in day E15 muscle. A high molecular weight polypeptide, distinct from the alpha and beta proteins, is recognized by antifoot protein antibodies. This polypeptide is observed in day E8 muscle and declines in abundance with continued development. It appears to exist as a monomer and does not bind [3H]ryanodine. In contrast, the alpha isoform present in day E10 muscle and the beta isoform in day E20 muscle are oligomeric and bind [3H]ryanodine suggesting that they may exist as functional calcium channels in differentiating muscle. Comparison of the intracellular distributions of the alpha foot protein, f-actin, the heavy chain of myosin and titin in day E10 muscle indicates that the alpha foot protein is expressed during myofibril assembly and Z line formation. The differential expression of the foot protein isoforms in developing muscle, and their continued expression in mature muscle, is consistent with these proteins making different functional contributions. In addition, the expression of the alpha isoform during the time of organization of a differentiated muscle morphology suggests that foot proteins may participate in events involved in muscle differentiation.
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PMID:Foot protein isoforms are expressed at different times during embryonic chick skeletal muscle development. 202 50

Mouse L929 cells were used to study the mechanism of cAMP induction of alkaline phosphatase (AP) activity. Following treatment with 200 microM 8-chlorophenylthio-cAMP (CPT-cAMP), alkaline phosphatase enzyme activity was observed to increase 80-fold after 24 h. The CPT-cAMP dose response of the alkaline phosphatase enzyme activity correlated well with the CPT-cAMP activation of cAMP-dependent protein kinase in L cells. A cDNA clone for the alkaline phosphatase was isolated and used to demonstrate a 10-fold increase in alkaline phosphatase mRNA levels after a 24-h treatment of L cells with CPT-cAMP. Increased mRNA levels were first detected 4-6 h, after CPT-cAMP treatment, and the level of alkaline phosphatase mRNA decreased rapidly after removal of CPT-cAMP. In vitro nuclear transcription studies showed that a 3-fold increase in alkaline phosphatase gene transcription was detectable 6 h after CPT treatment, and this increase was blocked by cycloheximide. In order to determine if the catalytic (C) subunit of cAMP-dependent protein kinase was able to mediate the induction of AP, L cells were transfected with expression vectors containing the metallothionein promoter and coding for the C alpha isoform of the catalytic subunit of cAMP-dependent protein kinase or for a catalytic subunit in which lysine 72 had been mutated to methionine (C alpha K72M). Zinc treatment of stably transfected cells expressing the wild-type C subunit showed an increase in protein kinase activity and an increase in AP activity. Zinc treatment of cells containing the mutant C subunit expression vector produced an increase in the amount of a protein which was recognized by C subunit antibodies on Western blots, but these cells showed no increase in protein kinase activity or in AP activity. We conclude that the C subunit is sufficient for transcriptional induction of the AP gene and that the phosphotransferase activity of the C subunit is required for this induction.
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PMID:Induction of alkaline phosphatase in mouse L cells by overexpression of the catalytic subunit of cAMP-dependent protein kinase. 216 96

In photoreceptors, Na+, K(+)-ATPase maintains the ion gradients which power the dark current that sustains the response to light. The enzyme is composed of at least two polypeptides: alpha (the catalytic subunit) and beta. Three different isoforms of the alpha subunit and two isoforms of the beta subunit have been identified in rat. In some tissues, the isoenzymes have been shown to be differentially expressed during development or in response to varying physiological conditions. RNAs prepared from isolated photoreceptors and from whole retina were analyzed on blots that were hybridized with cDNA probes for the alpha 1, alpha 2, alpha 3, beta 1 and beta 2 isoforms. The predominant alpha and beta subunit mRNAs present in the photoreceptor preparation were those encoding the alpha 3 and beta 2 isoforms, accounting for 85% of the total alpha signal and 79% of the total beta signal, respectively. Proportions of each mRNA were similar in retina, but very different from those observed in two control tissues, brain and kidney. To confirm that the alpha-subunit mRNA species detected were translated, membranes prepared from isolated photoreceptors and whole retina were examined by immunoblotting. The antibodies detected a pattern of alpha isoform distribution in these tissues and in kidney and brain controls that agreed remarkably well with the pattern of mRNA expression in the same tissues. Moreover, the alpha 3 isoform was detectable in the inner segment plasma membrane of the photoreceptor by electron microscopic immunocytochemistry. These results indicate that alpha 3, and beta 2 are the predominant isoforms of Na+, K(+)-ATPase expressed in photoreceptors and retina.
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PMID:Na+, K(+)-ATPase of the photoreceptor: selective expression of alpha 3 and beta 2 isoforms. 217 74

The heterogeneity of the protein kinase C (PKC) gene family strongly suggests that different isoforms may have distinct functions in mediating signal transduction. However, there is very little direct evidence for this. PKC has been implicated in arachidonate (AA) release in many cell types. We sought to investigate whether bradykinin- and phorbol ester-stimulated AA release in Madin-Darby canine kidney (MDCK) cells was correlated with differential activation of PKC isoforms. Using phorbol esters to (i) activate the enzyme and (ii) to down-regulate it, we report that differential activation (translocation) of PKC alpha is associated with AA release in MDCK cells and that specific down-regulation of PKC alpha is associated with a loss of AA release in response to stimulation with dioctanoylglycerol and phorbol ester. We also demonstrate that bradykinin-stimulated AA release was associated with differential activation of PKC alpha and was inhibited in PKC alpha down-regulated cells. Thus, we conclude that the PKC alpha isoform is likely to be responsible for mediating AA release in these cells.
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PMID:Differential activation of protein kinase C alpha is associated with arachidonate release in Madin-Darby canine kidney cells. 234 88

The replication of simian virus 40 (SV40) DNA is dependent upon a single viral protein [tumor (T) antigen] and multiple cellular proteins. To define the required cellular proteins, we have made use of a cell-free system that supports the replication of plasmid DNA molecules containing the SV40 origin of replication. We report here the purification from HeLa cell extracts of replication protein C (RP-C), a previously undescribed protein that is required to reconstitute efficient DNA replication in vitro. Highly purified preparations of RP-C contain two closely related polypeptides of 32 and 34 kDa. Preincubation of purified RP-C with T antigen and the DNA template largely eliminates the delay normally observed before the onset of rapid DNA synthesis. In addition, RP-C stimulates the unwinding of duplex DNA molecules containing the SV40 replication origin in a reaction that requires T antigen and a single-stranded DNA binding protein. These observations suggest that RP-C is involved in the initial steps of SV40 DNA replication in vitro.
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PMID:Purification of replication protein C, a cellular protein involved in the initial stages of simian virus 40 DNA replication in vitro. 254 40

A synthetic peptide of 18 amino acids corresponding to the inhibitory domain of the heat-stable protein kinase inhibitor was synthesized and shown to inhibit both the C alpha and C beta isoforms of the catalytic (C) subunit of cAMP-dependent protein kinase. Extracts from cells transfected with expression vectors coding for the C alpha or the C beta isoform of the C subunit required 200 nM protein kinase inhibitor peptide for half-maximal inhibition of kinase activity in extracts from these cells. An affinity column was constructed using this synthetic peptide, and the column was incubated with protein extracts from cells overexpressing C alpha or C beta. Elution of the affinity column with arginine allowed single step isolation of purified C alpha and C beta subunits. The C alpha and C beta proteins were enriched 200-400-fold from cellular extracts by this single step of affinity chromatography. No residual inhibitory peptide activity could be detected in the purified protein. The purified C subunit isoforms were used to demonstrate preferential antibody reactivity with the C alpha isoform by Western blot analysis. Furthermore, preliminary characterization showed both isoforms have similar apparent Km values for ATP (4 microM) and for Kemptide (5.6 microM). These results demonstrate that a combination of affinity chromatography employing peptides derived from the heat-stable protein kinase inhibitor protein and the use of cells overexpressing C subunit related proteins may be an effective means for purification and characterization of the C subunit isoforms. Furthermore, this method of purification may be applicable to other kinases which are known to be specifically inhibited by small peptides.
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PMID:Affinity purification of the C alpha and C beta isoforms of the catalytic subunit of cAMP-dependent protein kinase. 255 18

We have made use of the cell-free SV40 DNA replication system to identify and characterize cellular proteins required for efficient DNA synthesis. One such protein, replication protein C (RP-C), was shown to be involved with SV40 large T antigen in the early stages of viral DNA replication in vitro. We demonstrate here that RP-C is identical to the catalytic subunit of cellular protein phosphatase 2A (PP2Ac). The purified protein dephosphorylates specific phosphoamino acid residues in T antigen, consistent with the hypothesis that SV40 DNA replication is regulated by modulating the phosphorylation state of the viral initiator protein. We also show that purified RP-C/PP2Ac preferentially stimulates SV40 DNA replication in extracts from early G1 phase cells. This finding suggests that the activity of a cellular factor that influences the net phosphorylation state of T antigen is cell cycle dependent.
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PMID:Activation of SV40 DNA replication in vitro by cellular protein phosphatase 2A. 255 76

Mouse epidermal cytosol contains a protein phosphatase with Mr 38,000, which dephosphorylates the elongation factor 2 (EF-2) of protein biosynthesis and is stimulated after topical application of TPA to mouse skin [(1988) Biochem. Biophys. Res. Commun. 153, 1129-1135]. Dephosphorylation of EF-2 by this phosphatase is inhibited by okadaic acid at concentrations as low as 10(-8) M, but not by heparin up to concentrations of 600.micrograms/ml. The catalytic subunit of protein phosphatase 2A (PP2Ac) with EF-2 as a substrate exhibits the same sensitivity towards okadaic acid and insensitivity towards heparin as the EF-2 phosphatase of epidermal cytosol. The catalytic subunit of protein phosphatase 1 (PP1c) is strongly suppressed by heparin and less sensitive towards okadaic acid than PP2Ac. PP2Ac is around 50 times more efficient in dephosphorylating EF-2 than PP1c. These data indicate that the TPA-stimulated EF-2 phosphatase in epidermal cytosol is a type 2A protein phosphatase.
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PMID:A type 2A protein phosphatase dephosphorylates the elongation factor 2 and is stimulated by the phorbol ester TPA in mouse epidermis in vivo. 255 20

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