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)

Rats were exposed to 12% O2 (1 atm) for 48 hr, then 10% O2 for the duration of the exposures. Significant elevations in enzymes of the glutathione peroxidase system were found in the lungs of rats killed 3.5, 7.5, and 12.5 days of exposure compared to air-breathing controls. Superoxide dismutase was also elevated after hypoxia but nonsignificantly. Animals killed 12.5 days after exposures exhibited 75% (P less than 0.05) more thiobarbituric acid reactive products in their lungs compared to controls. These results along with significant increases of lung lipid peroxidation and in an augmentation of protective antiperoxidative lung defense capabilities. Hypoxia also resulted in enzyme elevations of lung phosphofructokinase and pyruvate kinase, which may indicate an adaptive increase in lung glycolytic capabilities which would be helpful in maintaining lung tissue energy requirements during hypoxia. In addition, it was confirmed that red blood cell count, hemoglobin and hematocrit values increased after prolonged hypoxia. The results of this study might also reflect enzyme elevation/induction due to cellular reparative-proliferative processes following hypoxia.
Exp Mol Pathol 1986 Dec
PMID:Selected pulmonary biochemical and hematological changes produced by prolonged hypoxia in the rat. 294 10

The livers of streptozotocin-induced diabetic and fasted rats showed a decreased cholesterol synthesis measured by in vitro incorporation of [2-14C]acetate. A significant decrease of glucose-6-phosphate dehydrogenase (G-6-PD), 6-phosphogluconate dehydrogenase (6-PGD), and pyruvate kinase (PK) was also observed 7 days after administration of streptozotocin. These enzymatic activities were also low in livers of 72 hr fasted animals. An increase of glucose-6-phosphatase (G-6-Pase) was observed consistently in diabetic as well as in fasted rats. Suitable amounts of insulin and refeeding normalized the alterated enzymatic activities in diabetic and in fasted animals, respectively.
Exp Mol Pathol 1985 Oct
PMID:Hexose monophosphate shunt and cholesterol synthesis in the diabetic and fasting states. 299 16

Pancreatic islet cytosol contains a calcium-calmodulin dependent protein kinase that can mediate the phosphorylation of an endogenous protein that has an Mr of 57 000, as well as exogenous muscle pyruvate kinase (subunit Mr, 57 000). EGTA and trifluoperazine decreased the phosphorylation. Alkaline inactivation of pyruvate kinase made it a better substrate for the kinase. As in rat islet cytosol, rabbit islet cytosol catalyzed the phosphorylation of a 57 000 Mr protein in the presence of calcium and calmodulin. This phosphoprotein was immunoprecipitated with anti-pyruvate kinase antibody. This is consistent with the idea that the 57 000 Mr phosphoprotein in islet cytosol is the subunit of pyruvate kinase. The paper following this paper shows that the kinetic and immunologic properties of the islet pyruvate kinase indicate it is the M2 isoenzyme and that its phosphorylation does not affect its catalytic activity.
Mol Cell Biochem 1985 Oct
PMID:Evidence for calcium enhanced phosphorylation of pyruvate kinase by pancreatic islets. 300

Leishmania donovani promastigotes contain intense tartrate-resistant cell surface acid phosphatase (ACP1) which blocks superoxide anion production by activated human neutrophils [A.T. Remaley et al. (1984) J. Biol. Chem, 259, 11173-11175]. An extensively purified preparation of ACP1 dephosphorylates several phosphoproteins which are phosphorylated at serine residues; these include: pyruvate kinase (Km 1.6 microM; Vmax 71.4 U (mg protein)-1), phosphorylase kinase (Km 0.076 microM; Vmax 5.4 U (mg protein)-1) and histones (Km 4.86 microM; Vmax 2.2 U (mg protein)-1). However, the specific activity of the leishmanial phosphatase on these phosphoproteins is very low as compared to other phosphoprotein phosphatases. The phosphatase activity of ACP1 was also low on phosphohistone phosphorylated at tyrosine residues. Phosphatidylinositol-4,5-diphosphate (PIP2) and inositoltriphosphate (IP3) were also tested as ACP1 substrates. PIP2 was hydrolyzed rapidly by ACP1. The rate of hydrolysis of PIP2 was higher at pH 6.8 (Km 2.35 microM; Vmax 107 X 10(3) U (mg protein)-1) than at pH 5.5 (Km 4.16 microM; Vmax 71 X 10(3) U (mg protein)-1). 32P-labeled IP3 was also a substrate for ACP1; the hydrolysis products consisted of a mixture of inositoldiphosphate and inositolmonophosphate. ACP1 and ten other phosphatases were tested for their ability to dephosphorylate proteins and to inhibit O2- production by stimulated human neutrophils. There was no correlation between the protein phosphatase activity of the acid- and alkaline phosphatases and their ability to block neutrophil O2- production. The results indicate that ACP1 probably blocks the production of reduced oxygen intermediates by a mechanism that does not involve dephosphorylation of phosphoproteins; however, the possibility that the parasite's phosphatase affects phagocyte metabolism by degrading PIP2 or IP3 should be considered.
Mol Biochem Parasitol 1986 Aug
PMID:Hydrolysis of phosphoproteins and inositol phosphates by cell surface phosphatase of Leishmania donovani. 301 59

We identified and characterized two regions of the human c-myc protein that target proteins into the nucleus. Using mutant c-myc proteins and proteins that fuse portions of c-myc to chicken muscle pyruvate kinase, we found that residues 320 to 328 (PAAKRVKLD; peptide M1) induced complete nuclear localization, and their removal from c-myc resulted in mutant proteins that distributed in both the nucleus and cytoplasm but retained rat embryo cell cotransforming activity. Residues 364 to 374 (RQRRNELKRSP; peptide M2) induced only partial nuclear targeting, and their removal from c-myc resulted in mutant proteins that remained nuclear but were cotransformationally inactive. We conjugated synthetic peptides containing M1 or M2 to human serum albumin and microinjected the conjugate into the cytoplasm of Vero cells. The peptide containing M1 caused rapid and complete nuclear accumulation, whereas that containing M2 caused slower and only partial nuclear localization. Thus, M1 functions as the nuclear localization signal of c-myc, and M2 serves some other and essential function.
Mol Cell Biol 1988 Oct
PMID:Identification of the human c-myc protein nuclear translocation signal. 305 8

The pyruvate kinase of Trypanosoma brucei can be purified to homogeneity in one step by affinity elution from a phosphocellulose column with the substrate phosphoenolpyruvate (PEP) and the allosteric activator fructose-2,6-diphosphate (FDP). The purified enzyme has a specific activity of 175 mumol min-1 (mg protein)-1 and a subunit molecular mass of 59 kDa as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Kinetic studies of the pure enzyme show that an increase in the PEP concentration decreases the apparent Km for adenosine diphosphate (ADP) and that an increase in the ADP concentration decreases the half saturation point (S0.5) for PEP. Likewise, the allosteric activator FDP decreases both the apparent Km for ADP and the S0.5 for PEP. ADP concentrations above 0.2 mM inhibit trypanosomal pyruvate kinase.
Mol Biochem Parasitol 1988 Nov
PMID:Purification in a single step and kinetic characterization of the pyruvate kinase of Trypanosoma brucei. 318 19

The total sequence of a 13,021 base-pair (bp) genomic fragment containing the rat L-type pyruvate kinase (L-PK) gene was determined by "shot gun" sequencing. This fragment includes 8360 bp of the L-PK gene, plus 3193 bp of the 5'-flanking and 1468 bp of the 3'-flanking regions. Like the chicken PK-M1 gene, the rat L-PK gene exhibits a fully conserved exon-intron structure, with 11 exons and 10 introns. In the chicken M1 gene, the coding sequences are well conserved (about 70%), in particular at the level of the exons implicated in the formation of PK active sites, exons that are also partially homologous to the corresponding sequences of the yeast gene. Various types of repetitive sequences exist in the L-PK gene, especially two ID (identifier) sequences located in the second intron and the 11th exon. Elements very similar to the "cyclic AMP-dependent regulatory element" recently described in the phosphoenolpyruvate carboxykinase and somatostatin genes are found in the sequenced fragment, but far upstream (-2338) and downstream (+5788) from the cap site. Various sequences homologous to described regulatory elements (glucocorticoid regulatory elements, enhancers, potential Z-DNA) are also observed 5' and 3' of the cap site. A comparison of the 5'-flanking region of the L-PK gene with the same regions of liver-specific or non-specific, cyclic-AMP-responsive or non-responsive genes was also made. It revealed various potentially interesting features that will be used to guide a further functional study. The cap site was determined by primer extension and nuclease S1 mapping using either mature mRNA or precursor RNA as templates. With both templates the start site of transcription appeared to be microheterogeneous, 19 to 14 bp before the ATG translation initiation codon.
J Mol Biol 1987 Jul 05
PMID:Structure of the rat L-type pyruvate kinase gene. 330 48

The v-vis gene encodes p28sis, the transforming protein of simian sarcoma virus. This gene resulted from a fusion of the env gene of simian sarcoma-associated virus and the woolly monkey gene for the B chain of platelet-derived growth factor (PDGF). Previous work has shown that the v-sis gene product undergoes signal sequence cleavage, glycosylation, dimerization, and proteolytic processing to yield a secreted form of the protein. It transport across the endoplasmic reticulum is blocked by the introduction of a charged amino acid residue within the signal sequence, the protein does not dimerize, is not secreted, and is no longer transforming as assayed by focus-forming ability in NIH 3T3 cells. Instead, this mutant protein localizes to the nucleus as demonstrated by both indirect immunofluorescence and cell fractionation. Using a series of deletion mutations, we delimited an amino acid sequence within this protein which is responsible for nuclear localization. This region is completely conserved in the predicted human c-sis protein, although it lies outside of regions required for transformation by the v-sis gene product. This nuclear transport signal is contained within amino acid residues 237 to 255, RVTIRTVRVRRPPKGKHRK. An amino acid sequence containing these residues is capable of directing cytoplasmic v-sis mutant proteins to the nucleus. This sequence is also capable of directing less efficient nuclear transport of a normally cytoplasmic protein, pyruvate kinase. Pulse-chase experiments indicate that the half-lives of nuclear and cytoplasmic v-sis mutant proteins are approximately 35 min. Using the heat-inducible hsp70 promoter from Drosophila melanogaster, we showed that the nuclear v-sis protein accumulates in the nucleus within 30 min of induction. The identification of a nuclear transport signal in the v-sis gene product raises interesting questions regarding the possibility of some function for PDGF or PDGF-related molecules in the nucleus.
Mol Cell Biol 1987 Oct
PMID:Identification of a signal for nuclear targeting in platelet-derived-growth-factor-related molecules. 331 80

The effects of ligands on the structure of rabbit muscle pyruvate kinase were studied by small angle neutron scattering. The radius of gyration, RG, decreases by about 1 A in the presence of the substrate phosphoenolpyruvate, but increases by about the same magnitude in the presence of the allosteric inhibitor phenylalanine. With increasing pH or in the absence of Mg2+ and K+, the RG of pyruvate kinase increases. Hence, there is a 2-A difference in RG between two alternative conformations. Length distribution analysis indicates that, under all experimental conditions which increase the radius of gyration, there is a pronounced increase observed in the probability for interatomic distance between 80 and 110 A. These small angle neutron scattering results indicate a "contraction" and "expansion" of the enzyme when it transforms between its active and inactive forms. Using the alpha-carbon coordinates of crystalline cat muscle pyruvate kinase, a length distribution profile was calculated, and it matches the scattering profile of the inactive form. These observations are expected since the crystals were grown in the absence of divalent cations (Stuart, D. I., Levine, M., Muirhead, H., and Stammers, D. K. (1979) J. Mol. Biol. 134, 109-142). Hence, results from neutron scattering, x-ray crystallographic, and sedimentation studies (Oberfelder, R. W., Lee, L. L.-Y., and Lee, J.C. (1984) Biochemistry 23, 3813-3821) are totally consistent with each other. With the aid of computer modeling, the crystal structure has been manipulated in order to effect changes that are consistent with the conformational change described by the solution scattering data. The structural manipulation involves the rotation of the B domain relative to the A domain, leading to the closure of the cleft between these domains. These manipulations resulted in the generation of new sets of atomic (C-alpha) coordinates, which were utilized in calculations, the result of which compared favorably with the solution data.
 ...
PMID:Domain interaction in rabbit muscle pyruvate kinase. II. Small angle neutron scattering and computer simulation. 334 33

The pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) of Leishmania major promastigotes is a multimer of 59 kDa subunits having an Mr 181000. It is activated by its substrate phosphoenolpyruvate (PEP) in a positively cooperative manner, and heterotropically by fructose 1,6-bisphosphate (FBP). Kinetics with regard to the phosphate acceptor adenosine 5'-diphosphate (ADP), MgCl2, and KCl are hyperbolic and unaffected by FBP. The enzyme is strongly inhibited by the reaction product ATP, as well as GTP and ITP, and to a lesser degree by citrate. Of seven amino acids reported to inhibit the pyruvate kinases of other organisms, none have any effect on the L. major pyruvate kinase in vitro. The enzyme shows its maximum activity at pH 7.0 in the absence of FBP, and at pH 7.6 in its presence. Contrary to previous suggestions, the enzyme appears to be well-suited for a regulatory role in the metabolism of an aerobic organism capable of net glucose synthesis.
Mol Biochem Parasitol 1988 Jan 15
PMID:Purification and characterization of a metabolite-regulated pyruvate kinase from Leishmania major promastigotes. 334 4


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