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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years it has become apparent that an increasing number of proteins can be phosphorylated at several different sites. In this article protein multisite phosphorylation is discussed with reference to the enzymes glycogen synthase, pyruvate dehydrogenase, and phosphorylase kinase. Each of these enzymes contains three or more different phosphorylation sites on one or more subunits. Activation and inactivation of the enzymes appear to correlate quite well with phosphorylation of a few key sites on the protein. The other phosphorylation sites may influence other kinetic properties of the enzymes or regulate the rates of dephosphorylation of the key sites by the appropriate phosphatase. Thus, multisite phosphorylation may represent an important mechanism for regulating several functions of complex proteins.
Mol Cell Endocrinol 1979 Dec
PMID:Regulatory functions of protein multisite phosphorylation. 23 Jan 3

A model for microsomal glucose 6-phosphatase (EC 3.1.3.9) is presented. Glucose 6-phosphatase is postulated to be resultant of the coupling of two components of the microsomal membrane: 1) a glucose 6-phosphate - specific transport system which functions to shuttle the sugar phosphate from the cytoplasm to the lumen of the endoplasmic reticulum; and 2) a catalytic component, glucose-6-P phosphohydrolase, bound to the luminal surface of the membrane. A large body of existing data was shown to be consistent with this hypothesis. In particular, the model reconciles well-documented differences in the kinetic properties of the enzyme of untreated and modified microsomal preparations. Characteristic responses of the enzyme to changes in nutritional and hormonal states may be attributed to adaptations which alter the relative capacities of the transport and catalytic components.
Mol Cell Biochem 1975 Feb 28
PMID:On the involvement of a glucose 6-phosphate transport system in the function of microsomal glucose 6-phosphatase. 23 36

1. Marker enzymes for the principal subcellular organelles of rat liver were asayed in the liver of rats 1 day and 8 days after bile-duct ligation or after laparotomy as a control procedure. 2. The microsomal enzymes in liver tissue showed complex changes. Benz[alpha]pyrene hydroxylase activity, predominantly found in the smooth endoplasmic reticulum, was decreased. Glucose 6-phosphatase activity and ribonucleic acid, which are localized predominantly in the rough endoplasmic reticulum, were increased. 3. The plasma membrane enzyme, alkaline phosphatase, increased in activity after bile-duct ligation. 4. No changes in mitochondrial enzyme activities were noted after 1 day but there was a 50% reduction 8 days after ligation. Lysosomal enzyme activities did not change in the liver tissue. 5. Liver catalase and D-amino acid oxidase activities showed a slight increase at 1 day postligation but a significant fall by 8 days. 6. Lactate dehydrogenase, a cytosol enzyme, showed a decrease in activity after 1 day but an increase in tissue activities 8 days after ligation. 7. Serum activities of mitochondrial, plasma membrane, microsomal, lysosomal and cytosol marker enzymes tended to increase post-ligation, particularly at 8 days. 8. Monoamine oxidase, a predominantly mitochondrial enzyme, was greatly elevated in the serum after 1 day but had returned to normal activities by 8 days.
Clin Sci Mol Med 1975 Apr
PMID:Effect of bile-duct ligation on organelle marker enzymes in the liver and serum of rats. 23 11

The nature of the 5'-termini in pre-mRNA isolated from Ehrlich carcinoma cells has been investigated. To discriminate between triphosphorylated 5'-ends and capped structures different methods were used including treatment by alkaline phosphatase and several chromatographic methods. It was shown that heavey pre-mRNA contains a significant number of non-blocked triphosphorylated nucleotides at the 5'-end termini. However, phosphatase resistent, blocked 5'-termini were also found. 5'-terminal nucleotides in triphosphorylated pre-mRNA are G in a 3 : 2 ratio. In contrast to nuclear pre-mRNA cytoplasmic poly(A)+mRNA does not contain triphosphorylated 5'-ends but does contain the "cap" structure only. To elucidate the pre-mRNA topography the localization of homopolymeric regions of pre-mRNA, poly(A) and oligo(U), in relation to 5'terminal structures has been investigated. The experiments showed that the distance between 3'-terminal poly(A) sequences and 5'-end triphosphates is longer than 1500--2000 nucleotides. At the same time the distance between the latter and oligo(U) in pre-mRNA is much shorter.
Mol Biol (Mosk)
PMID:[Structure of nuclear pre-mRNA. XI. Triphosphorylated and blocked 5'-ends in the pre-mRNA]. 46 Jan 97

Phenotypes of the cells developing into small colonies after days of primary culture of adult rat hepatocytes in serum-free modified Dulbecco Modified Eagles' medium containing 10 mM nicotinamide and 10 ng/ml epidermal growth factor were analyzed immunocytochemically, cytochemically and ultrastructurally. Albumin, cytokeratin 8 and 18 were seen by immunocytochemical techniques in the cells of the small colonies at Day 6. Transferrin, alpha 1-antitrypsin, ceruloplasmin, and haptoglobin, proteins secreted by mature hepatocytes, were faintly stained in these cells as was alpha-fetoprotein. These proteins were secreted into the culture medium as evidenced by immunoblot analysis. gamma-Glutamyltransferase, alkaline phosphatase and glucose 6-phosphatase were not present in the cells of the small colonies as well as the surrounding hepatocytes at Day 6 of culture. In addition, ultrastructural examinations of the cells in the small colonies indicated that these cells not only had many characteristic mitochondria and desmosomes, but also a few small peroxisomes. Such cells, even after 20 days in culture were proliferating, as evidenced by the intranuclear presence of the proliferating cell nuclear antigen. The potential relation of these cells to hepatocytes which may serve as the principal reserve for replicating hepatocytes is discussed.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Characteristics of small cell colonies developing in primary cultures of adult rat hepatocytes. 127 92

The retinoblastoma tumor suppressor gene product (pRb) is a nuclear protein subject to cell cycle-regulated hyperphosphorylation. I constructed a recombinant vaccinia virus vector that expresses both the underphosphorylated and hyperphosphorylated forms of pRb and purified the recombinant protein by using immunoaffinity chromatography directed toward a synthetic carboxy-terminal epitope. To investigate the hypothesis that hyperphosphorylation of pRb is a means of controlling its growth-regulating activity, I tested purified pRb for the ability to be reincorporated into pRb-deficient nuclei in vitro. The underphosphorylated form of pRb efficiently reassociated with nuclei, but the hyperphosphorylated form remained soluble in this assay. Nuclear binding of pRb was enhanced by phosphatase treatment and reduced by phosphorylation of pRb effected by using a preparation of the cell cycle-regulatory kinase p34cdc2. Mutant-encoded proteins with altered E1A-binding domains failed to bind to nuclei. Pretreatment of target nuclei with nucleases and high-salt extraction did not alter the specificity of binding for underphosphorylated pRb. These observations demonstrate that hyperphosphorylation of pRb can regulate its interaction with nuclei, supporting the hypothesis that hyperphosphorylation controls the growth-regulatory activities of pRb. Further, at least one target of pRb binding appears to be an integral component of the nuclear envelope.
Mol Cell Biol 1992 Feb
PMID:Nuclear binding of purified retinoblastoma gene product is determined by cell cycle-regulated phosphorylation. 131 Jan 46

To determine how the human cdc25 gene product acts to regulate p34cdc2 at the G2 to M transition, we have overproduced the full-length protein (cdc25Hs) as well as several deletion mutants in bacteria as glutathione-S-transferase fusion proteins. The wild-type cdc25Hs gene product was synthesized as an 80-kDa fusion protein (p80GST-cdc25) and was judged to be functional by several criteria: recombinant p80GST-cdc25 induced meiotic maturation of Xenopus oocytes in the presence of cycloheximide; p80GST-cdc25 activated histone H1 kinase activity upon addition to extracts prepared from Xenopus oocytes; p80GST-cdc25 activated p34cdc2/cyclin B complexes (prematuration promoting factor) in immune complex kinase assays performed in vitro; p80GST-cdc25 stimulated the tyrosine dephosphorylation of p34cdc2/cyclin complexes isolated from Xenopus oocyte extracts as well as from overproducing insect cells; and p80GST-cdc25 hydrolyzed p-nitrophenylphosphate. In addition, deletion analysis defined a functional domain residing within the carboxy-terminus of the cdc25Hs protein. Taken together, these results suggest that the cdc25Hs protein is itself a phosphatase and that it may function directly in the tyrosine dephosphorylation and activation of p34cdc2 at the G2 to M transition.
Mol Biol Cell 1992 Jan
PMID:cdc25+ encodes a protein phosphatase that dephosphorylates p34cdc2. 131 80

Na+,K(+)-ATPase is a major determinant of myocyte homeostasis and excitation-contraction. Cardiac glycosides such as digitalis and ouabain increase the inotropic state of the heart through the inhibition of Na+,K(+)-ATPase. While cardiac glycosides are commonly used in the setting of congestive heart failure, optimal therapy would depend upon an intact Na+,K(+)-ATPase system. Changes in Na+,K(+)-ATPase activity and glycoside receptor density with the development of cardiomyopathy have not been well defined. Accordingly, left ventricular (LV) function and Na+,K(+)-ATPase activity and glycoside binding were examined in 7 pigs with dilated cardiomyopathy and in 7 controls. Dilated cardiomyopathy was produced by pacing induced supraventricular tachycardia (SVT) for 3 weeks at 240 bpm. Left ventricular function was examined by simultaneous echocardiography and catheterization. Left ventricular fractional shortening significantly decreased with SVT (34 +/- 2 vs. 10 +/- 2%, P less than 0.05) and LV diastolic dimension and pressure significantly increased (3.8 +/- 0.3 vs. 5.1 +/- 0.4 cm, and 8 +/- 2 vs. 27 +/- 2 mmHg, respectively, P less than 0.05) as compared to controls. Na+,K(+)-ATPase activity was assayed as potassium dependent p-nitrophenol-phosphatase activity. Glycoside receptor density (Bmax) and affinity (KD) was determined using [3H]-ouabain binding assays. Na+,K(+)-ATPase activity, Bmax, and KD all significantly fell from control values with SVT induced cardiomyopathy (0.64 +/- 0.06 vs. 0.45 +/- 0.12 micrograms pNP/mg/h, 5.5 +/- 0.4 vs. 1.9 +/- 0.4 pmol/mg, and 15 +/- 3 vs. 9 +/- 3 nM, respectively, P less than 0.05). The distribution of Na+,K(+)-ATPase in LV sections taken from control and SVT hearts were examined using immunohistochemical techniques. A patchy distribution of Na+,K(+)-ATPase along the sarcolemma in SVT sections was observed as opposed to a more uniform distribution in control myocytes. There was no observable change in the relative content and distribution of the Na+,K(+)-ATPase isoforms alpha 2 and alpha 3 in the SVT sections as compared to controls. In an additional set of experiments, changes in LV as well as isolated myocyte responsiveness to ouabain were examined. Left ventricular fractional shortening and peak dP/dt were measured following administration of 20-60 micrograms/Kg of ouabain in control (n = 3) and SVT (n = 3) pigs. In the control group, 40 micrograms/Kg caused a 25% in LV fractional shortening and a 60% increase in peak dP/dt from baseline. Cumulative doses of 60 micrograms/Kg in the control pigs resulted in over a 75% increase in peak dP/dt from baseline values.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Cardiol 1992 Mar
PMID:Myocardial Na+,K(+)-ATPase in tachycardia induced cardiomyopathy. 132 Jul 3

Using cytostatic factor metaphase II-arrested extracts as a model system, we show that protein phosphatase 1 is regulated during early embryonic cell cycles in Xenopus. Phosphatase 1 activity peaks during interphase and decreases shortly before the onset of mitosis. A second peak of activity appears in mitosis at about the same time that cdc2 becomes active. If extracts are inhibited in S-phase with aphidicolin, then phosphatase 1 activity remains high. The activity of phosphatase 1 appears to determine the timing of exit from S-phase and entry into M-phase; inhibition of phosphatase 1 by the specific inhibitor, inhibitor 2 (Inh-2), causes premature entry into mitosis, whereas exogenously added phosphatase 1 lengthens the interphase period. Analysis of DNA synthesis in extracts treated with Inh-2, but lacking the A- and B-type cyclins, shows that phosphatase 1 is also required for the process of DNA replication. These data indicate that phosphatase 1 is a component of the signaling pathway that ensures that M-phase is not initiated until DNA synthesis is complete.
Mol Biol Cell 1992 Jun
PMID:Multiple roles for protein phosphatase 1 in regulating the Xenopus early embryonic cell cycle. 132 52

Protein phosphatase (PP2B) whose activity is stimulated 12-20-fold by Ca2+/calmodulin (CaM) was partially purified by CaM-Sepharose and heparin-agarose chromatographies from cell extract of the yeast Saccharomyces cerevisiae. PP2B activity was not detectable in a mutant in which two genes (CMP1 and CMP2) encoding homologs of mammalian PP2B catalytic subunit were disrupted. We have previously shown that the double gene disruption has no significant effect on the growth of yeast [1991, Mol. Gen. Genet. 227, 52-59]. The results indicated that CMP1 and CMP2 are the only genes that encode the PP2B catalytic polypeptide in S. cerevisiae, and PP2B activity is not essential for the growth of the yeast under normal conditions.
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PMID:Ca2+/calmodulin-activated protein phosphatase (PP2B) of Saccharomyces cerevisiae. PP2B activity is not essential for growth. 132 47


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