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)

Liver glycogen synthase b phosphatase, chromatographically separable from phosphorylase a phosphatase, is decreased in 48-hour alloxan diabetic rats. The phosphatase activities are measured in an in vitro system using exogenous isolated phospho-enzyme as substrates with added phosphatases. Synthase and phosphorylase phosphatases were shown to have differential catalytic properties by their reactivity in the presence of Pi, the heat-stable inhibitor of phosphorylase phosphatase and after incubation with added cAMP-dependent protein kinase.
Mol Cell Biochem 1979 May 06
PMID:Insulin sensitivity of liver glycogen synthase b into a conversion. 11 80

Plasma membranes have been prepared from porcine thyroid glands using sucrose gradients. The fractions having a density in sucrose of 1.18 g/ml mainly contained plasma membranes and were moderately contaminated with other subcellular components as shown by marker enzyme data. Purified plasma membranes incubated in the presence of [32-P]gamma ATP incorporated 32-P. Kinetics of incorporation of 32-P into endogenous substrates studied in various buffers and with increasing ATP concentration suggest a phosphodephosphorylating system related to cAMP-dependent protein kinase and phosphoprotein phosphatase activities. The two enzymatic activities associated with plasma membranes have been demonstrated using exogenous substrates. cAMP increases and fluoride ions decrease the extent of membrane phosphorylation. The specific activity of protein kinase was 10-12 times higher than in the initial homogenate and was only slightly enhanced in the presence of 0.5% Nonidet as compared to microsomal fraction. cAMP binding to membrane proteins was 3 times higher than to the other particulate fractions. TSH present in the incubating medium or added after 5 min of 32-P labelling induced a rapid stimulation of endogenous phosphorylation followed by a rapid decrease. Phosphorylated membrane substrates were analyzed: high voltage paper electrophoresis after partial hydrolysis indicated that [32-P]phosphate is incorporated into serine and threonine residues as o-phosphate derivatives. SDS-polyacrylamide gel electrophoresis showed several 32--labelled fractions. When enhanced by cAMP, no specific phosphorylation of protein components was observed.
Mol Cell Endocrinol 1975 May
PMID:Phosphorylation of purified thyroid plasma membranes incubated with [32-P]ATP. 16 13

The protein kinase activities of a transplantable, insulin-producing hamster islet cell tumor were characterized using gel filtration, sucrose density gradient centrifugation and acrylamide gel electrophoresis. The post-microsomal supernatant fluid contains 70-80% of the protein kinase activity present in crude homogenates. A cAMP-dependent protein kinase, PK I (Mr 170,000), represents 25% of the soluble protein kinase activity assayed with protamine as substrate. It dissociates in the presence of cAMP into a cAMP-binding protein, R2 (Mr 90,000) and a catalytic subunit C (Mr 33,000). The dissociation induced by cAMP seems to be facilitated by the addition of Mg2+ and ATP. The regulatory subunit, R2, changes its gel filtration pattern in the presence of 0.5 M NaCl suggesting dissociation into a smaller subunit, R1 (Mr 44,000). By analogy with purified beef heart protein kinase (Erlichman et al., 1973) and skeletal muscle protein kinase, PK I. The presence in crude homogenates of a free cAMP-binding protein indistinguishable from the R2 derived by dissociation of PK I, suggests that PK I is partially dissociated in vivo. A cAMP-independent (casein) kinase (Mr 210,000) elutes with PK I on columns of Sepharose 6B. Another cAMP-independent protein kinase, PK II (Mr 88,000), is the predominatn form of soluble protein kinase accounting for approximately 75% of the soluble protein kinase activity detected using protaimine as substrate. This cAMP-independent protein kinase changes its gel filtration pattern in the presence of 0.5 M NaCl giving rise to a form which appears to have the same Mr (33,000) as the catalytic subunit of PK I. Studies comparing the catalytic subunit C of PK I with PK II and its salt-induced smaller molecular form demonstrate facile association of C with the cAMP-binding protein of purified bovine heart protein kinase to yield a hybrid holoenzyme, whereas PK II and its smaller form fail to recombine in this fashion. The 33,000 dalton forms derived from PK I (by cAMP) and PK II (by salt) also show different substrate specificities. It would appear, therefore, that pK II is a cAMP-independent protein kinase unrelated to PK I.
Mol Cell Endocrinol 1976 Feb
PMID:Characterization of the protein kinases in a transplantable islet cell tumor of the Syrian hamster. 17 65

Two cAMP-dependent protein kinase activities can be separated from rat thyroid cytosol. Their elution properties during the gel chromatography, as well as their sedimentation coefficients after sucrose-gradient ultracentrifugation and their capacity to dissociate in the presence of histones, suggest they are like the Type I and Type II protein kinases described in many other tissues. The sensitivity of the two types of kinases to thyroxine treatment is different. The activity of Type I is not changed during the first 5 days of treatment. Thereafter, it decreased by about 50% and is maintained at that level for up to one month. The activity of the Type II enzyme decreased rapidly by about 30-40% already on the second day of treatment, and after 10 days it reached 50% of the initial level. This differential reactivity of the two types of enzymes to the thyroxine treatment leads to profound modifications in their relative activities between the second and the fifth day of treatment. The significance of these results and the possible role of the two types of kinases in the control of different steps of iodine metabolism have been discussed.
Mol Cell Endocrinol 1979 May
PMID:Hormonal regulation of thyroidal protein phosphokinase activities. II. Differential sensitivity of type I and type II cAMP-dependent enzymes to the treatment of rats with thyroxine. 22

The chicken ovalbumin gene is subject to multihormonal regulation. Maximal expression of it requires not only the synergistic effects of estrogen and corticosterone, but also the permissive effects of insulin. In addition to effects on transcription, the stability of its message is greatly enhanced by estrogen. Furthermore, two signal transduction pathways involving protein kinases have been implicated in the regulation of the ovalbumin gene. To better define the role of second messengers on expression of the ovalbumin gene, the effects of the protein kinase-C (PKC) and the cAMP-dependent protein kinase (PKA) pathways on the endogenous levels of ovalbumin mRNA and the transcription of an ovalbumin fusion gene were investigated. Primary cultures of oviduct cells were treated with phorbol 12-myristilate 13-acetate (an activator of PKC) or with forskolin and 3-isobutyl-1-methylxanthine (an activator of PKA) alone, activators plus estrogen and corticosterone, or activators plus both steroids and insulin. The results indicate that phorbol 12-myristilate 13-acetate causes a dramatic destabilization of ovalbumin message, resulting in a reduction in ovalbumin mRNA levels. In contrast, the activators of the PKA system can substitute for insulin and, thereby, increase expression of the ovalbumin gene synergistically with the steroids. The effect of the activators of the PKA system is at the level of transcription. Thus, in chicken oviduct cell cultures, the PKA and PKC signal transduction pathways act in opposing ways to modulate the steroid-induced expression of the ovalbumin gene.
Mol Endocrinol 1992 Sep
PMID:Regulation of expression of the chicken ovalbumin gene: interactions between steroid hormones and second messenger systems. 127 83

The signal transduction pathways of the dopamine-D1 receptor were investigated in two cell types stably transfected with the human D1 receptor cDNA, rat pituitary GH4C1 cells (GH4-hD1), and mouse Ltk-fibroblast cells (L-hD1). In both GH4-hD1 and L-hD1 cell lines, stimulation of the dopamine-D1 receptor induced a marked increase in cAMP accumulation. In addition, dopamine potentiated activation of L-type voltage-dependent calcium channels in a cAMP-dependent manner in GH4-hD1 cells. However, in L-hD1 cells, dopamine increased cytosolic free calcium concentrations ([Ca++]i) by mobilization of intracellular calcium rather than by calcium influx. This effect was correlated with a dopamine-induced enhancement of phospholipase C activity in L-hD1 cells. Pretreatment (24 h) with cholera toxin (CTX) was used to maximally activate the GTP-binding protein (G protein) Gs, causing a maximal elevation of cAMP levels and uncoupling the D1 receptor from Gs. The described actions of dopamine in both cell lines were abolished by pretreatment with CTX, indicating that CTX substrates (e.g. Gs) may mediate these actions. The blockade by CTX was not due to CTX-induced elevation of cAMP, since pretreatment with forskolin or 8-bromo-cAMP to activate cAMP-dependent protein kinase did not inhibit dopamine actions nor alter basal [Ca++]i. Pretreatment (1-3 h) of L-hD1 cells with forskolin (10 microM) or 8-bromo-cAMP (5 mM) altered neither the basal activity of phospholipase C nor basal [Ca++]i in L-hD1 cells but greatly enhanced the dopamine-induced increase of phosphatidyl inositol turnover and [Ca++]i. From these results we conclude that: 1) the dopamine-D1 receptor induces multiple and cell-specific signals, including elevation of cAMP levels in both GH and L cells, cAMP-dependent activation and potentiation of opening of L-type voltage-dependent calcium channel in GH cells, and a novel phosphatidyl inositol-linked mobilization of cellular calcium in L cells; 2) coupling of the D1 receptor to these responses involves CTX-sensitive proteins, possibly Gs; and 3) acute preactivation of cAMP-dependent protein kinase can markedly enhance, rather than attenuate, certain pathways of dopamine-D1 transmembrane signaling.
Mol Endocrinol 1992 Nov
PMID:Cholera toxin-sensitive 3',5'-cyclic adenosine monophosphate and calcium signals of the human dopamine-D1 receptor: selective potentiation by protein kinase A. 128 71

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

The aim of this study was to examine the possibility that atrial natriuretic peptide-stimulated testosterone production by mouse Leydig cells results from an activation of cAMP-dependent protein kinase (kinase A) by cGMP. In these cells, both 8Br-cGMP and 8Br-cAMP could stimulate testosterone production, though the latter was approximately 50-fold more potent. Following the stimulation of the cells with the atrial peptide, a dose-related decrease in the cellular protein-bound cAMP accompanied by a concomitant increase in the protein-bound cGMP was observed. The steroidogenesis stimulated by both human chorionic gonadotrophin (hCG) and atrial peptide was inhibited in a dose-dependent manner by a cAMP antagonist, adenosine 3',5'-cyclic monophosphothioate, Rp-isomer (RpcAMPS). In a cell-free [3H]cAMP binding assay, we have shown that unlabelled cGMP and RpcAMPS could competitively inhibit the [3H]cAMP binding, confirming that cAMP, RpcAMPS and cGMP could bind to the same binding protein. Finally, in a cell-free kinase A assay system, we have demonstrated that in lysates prepared from either atrial peptide or hCG-stimulated cells, the cellular kinase A was activated to an equal extent. We conclude from the data obtained that cGMP can bind to the cAMP-binding sites of kinase A and thereby brings about a promiscuous activation of this kinase. This appears to be an underlying mechanism by which atrial peptide hormone is able to stimulate the steroidogenesis in mouse Leydig cells.
Mol Cell Endocrinol 1992 Dec
PMID:Stimulation of testosterone production by atrial natriuretic peptide in isolated mouse Leydig cells results from a promiscuous activation of cyclic AMP-dependent protein kinase by cyclic GMP. 128 96

Myotonic dystrophy (DM) is associated with the expansion and instability of a trinucleotide (CTG) repeat in a sequence encoding a cAMP-dependent protein kinase. The normal copy number of 5-35 repeats is exceeded in DM patients, with the size of the expansion broadly correlating with the severity of symptoms experienced. In most families reported, the unstable DNA sequence has increased in size on transmission to affected offspring, thereby providing a molecular explanation for the phenomenon of anticipation in DM, i.e. an increase in the severity of symptoms associated with an earlier age at onset of the disease in successive generations of a family. Here we present the first reported case of a family where the transmission of the affected chromosome from father to son is accompanied by a reduction in the size of the triplet expansion, such that it falls within the normal range. As the son remains asymptomatic, this type of molecular event may provide an explanation for the incomplete penetrance of the disease phenotype reported for this disorder. The implications for genetic counselling of DM families and the mechanistic considerations of the trinucleotide instability are discussed.
Hum Mol Genet 1992 Oct
PMID:Unstable DNA may be responsible for the incomplete penetrance of the myotonic dystrophy phenotype. 130 46

In various species, including humans, 5-hydroxytryptamine (5-HT) has been shown to exert positive chronotropic and inotropic cardiac effects through different types of receptors. The goal of the present study was to investigate the regulation by 5-HT of voltage-gated Ca2+ channels in human atrial myocytes and to characterize the receptor involved. Cardiomyocytes isolated enzymatically and mechanically were voltage-clamped using the whole-cell configuration of the patch-clamp technique. Extracellular perfusion of 5-HT increased Ca2+ current (ICa) amplitude with a EC50 (0.1 microM) similar to that observed with isoprenaline. The effects of 5-HT were blocked by the addition of protein kinase A inhibitor in the pipette. In addition, the effects of 5-HT, isoprenaline, and intracellular cAMP on ICa were not additive. These results support the hypothesis that the inotropic effect of 5-HT in human atrial myocytes is related to an increase of ICa via an elevation of intracellular cAMP levels and stimulation of cAMP-dependent protein kinase. The effects of 5-HT were not blocked by antagonists of 5-HT1 (methiothepin), 5-HT2 (ketanserin), or 5-HT3 (ICS 205-930 at a low concentration) receptors. The benzamide derivatives renzapride and zacopride and the azabicyclobenzimidazolone derivative BIMU 8 increased ICa, but less efficiently than did 5-HT or 5-methoxytryptamine. Moreover, ICS 205-930 at high concentrations (greater than 1 microM) completely antagonized the effects of 5-HT. Thus, the pharmacology of the 5-HT receptor involved in an increase of ICa in human atrial myocytes resembles that recently described for the 5-HT4 receptor. In atrial myocytes dissociated from rat, rabbit, guinea pig, or frog, 5-HT at high concentrations had no effect on Ca2+ currents, suggesting that the distribution of 5-HT4 receptors in cardiac tissues is species dependent.
Mol Pharmacol 1992 Feb
PMID:Serotonin increases calcium current in human atrial myocytes via the newly described 5-hydroxytryptamine4 receptors. 131 10


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