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)

Slowing down of the rate of protein synthesis during ageing is accompanied by alterations in the amounts and activities of elongation factors, eEF-1 and eEF-2. Since the activity of eEF-2 is regulated by phosphorylation, we have determined the changes in the activities of eEF-2-specific phosphorylating and dephosphorylating enzymes during ageing. Previously, we have reported an age-related increase in the activity of eEF-2 kinase (BBRC, 192, 1210, 1993). We have now compared the activities of a dephosphorylating enzyme protein phosphatase 2A (PP2A) in young and old liver extracts from freely-fed or calorie-restricted rats. The activity of PP2A remain unaltered during ageing. Furthermore, there was no change in the kinetics and extent of PP2A-dependent and PP2A-independent dephosphorylation of eEF-2 during ageing.
Biochem Mol Biol Int 1995 Apr
PMID:Dephosphorylation of the phosphorylated elongation factor-2 in the livers of calorie-restricted and freely-fed rats during ageing. 762 35

A cDNA showing high sequence similarity (> 70%) to plant protein phosphatase 1 catalytic subunit variants from other species has been isolated from a cDNA library derived from mRNAs expressed in elicitor-treated suspension-cultured cells. The clone appears to be a near full-length 1431 bp with a 172 bp 5'-untranslated region and a 317 bp 3'-untranslated region. The open reading frame, determined by sequence similarity, codes for a protein with predicted M(r) of 35,552. Alternatively an ATG situated to the 5' end of the putative start site would increase the protein size by 6 amino acids. The mRNA for Pvpp1 was shown to be rapidly induced by elicitor treatment of suspension-cultured cells of French bean. The cloned cDNA represents one of the few examples of a gene product that is probably involved in dephosphorylation events arising after the initial responses to biotic stress.
Plant Mol Biol 1995 Jun
PMID:Molecular cloning of the cDNA encoding a stress-inducible protein phosphatase 1 (PP1) catalytic subunit from French bean (Phaseolus vulgaris L.). 763 8

The role of persistent protein phosphorylation upon gonadotropin releasing hormone (GnRH) stimulated luteinizing hormone (LH) release was investigated by the use of the selective inhibitors of protein phosphatase type 1 (PP1) and 2A (PP2A), okadaic acid (OA) and calyculin A. Pre-incubation of cultured rat pituitary cells with OA (24 h) or calyculin A (30 min) resulted in inhibition of GnRH-stimulated LH release with significant inhibition being detected at 10 nM and 30 nM for OA and calyculin A, respectively. The inactive OA analog norokadone and the protein tyrosine phosphatase inhibitor vanadyl hydroperoxide had no significant effect on GnRH-induced LH release. The stimulatory effects of the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol 13-acetate (TPA, 50 ng/ml) or the Ca2+ ionophore, ionomycin (1 micron), upon LH release were also abolished by pretreatment with OA (10-20 nM) or calyculin A (30 nM). Stimulation of LH release by high K+ (28 mM) or residual LH release stimulated by GnRH in Ca(2+)-free medium were also blocked by OA. These observations indicate that protein dephosphorylation is involved positively in GnRH-stimulated LH release. The site of action of the protein phosphatases PP1 and PP2A is most likely downstream to Ca2+ elevation and PKC activation by GnRH.
Mol Cell Endocrinol 1995 Apr 28
PMID:Involvement of protein phosphatases in gonadotropin releasing hormone regulated gonadotropin secretion. 764 55

To determine whether protein phosphatases can affect bone regulation, we examined the effects of okadaic acid (OA) and calyculin A (CA), specific inhibitors of protein phosphatases type 1 and type 2A, on alkaline phosphatase activity of mouse osteoblastic cells. Clone MC3T3-E1 cells were cultured with varying concentrations of OA and CA. OA and CA stimulated alkaline phosphatase (ALP) activity in the cells in dose-dependent fashion with a maximal effect at concentrations of 5 nM and 2 nM, respectively. The properties of OA-induced and native ALP in the cells were the same and they were liver-bone-kidney type. These results show that protein phosphatase inhibitors stimulate bone formation in vitro and that phosphorylation and dephosphorylation of specific proteins in the cells may be involved in bone regulation in vivo as well.
Biochem Mol Biol Int 1995 Jun
PMID:Protein phosphatase inhibitors, okadaic acid and calyculin A, induce alkaline phosphatase activity in osteoblastic cells derived from newborn mouse calvaria. 766 40

p44erk1 is a member of a family of tyrosyl-phosphorylated and mitogen-activated protein (MAP) kinases that participate in cell cycle control. A full-length erk1 cDNA was isolated from a human hepatoma cell line (Hep G2) library. The erk1 cDNA clone shared approximately 96% predicted amino acid identity with partial sequences of rodent erk1 cognates, and the erk1 gene was assigned to human chromosome 16 by hybrid panel analysis. Human erk1 expressed in Escherichia coli as a glutathione S-transferase fusion (GST-Erk1) protein was substantially phosphorylated on tyrosine in vivo. It underwent further autophosphorylation in vitro (up to 0.01 mol of P per mol) at the regulatory Tyr-204 site and at additional tyrosine and serine residues. Threonine autophosphorylation, presumably at the regulatory Thr-202 site, was also detected weakly when the recombinant kinase was incubated in the presence of manganese, but not in the presence of magnesium. Before and after cleavage of the GST-Erk1 protein with thrombin, it exhibited a relatively high level of myelin basic protein phosphotransferase activity, which could be reduced eightfold by treatment of the kinase with the protein-tyrosine phosphatase CD45, but not by treatment with the protein-serine/threonine phosphatase 2A. The protein-tyrosine kinase p56lck catalyzed phosphorylation of GST-Erk1 at two autophosphorylations sites, including Tyr-204, and at a novel site. A further fivefold stimulation of the myelin basic protein phosphotransferase activity of the GST-Erk1 was achieved in the presence of a partially purified MAP kinase kinase from sheep platelets. Under these circumstances, there was primarily an enhancement of the tyrosine phosphorylation of GST-Erk1. This MAP kinase kinase also similarly phosphorylated a catalytically compromised version of GST-Erk1 in which Lys-71 was converted to Ala by site-directed mutagenesis.
Mol Cell Biol 1993 Aug
PMID:Molecular cloning, expression, and characterization of the human mitogen-activated protein kinase p44erk1. 768 43

The immunosuppressants cyclosporin A (CsA) and FK506 appear to block T-cell function by inhibiting the calcium-regulated phosphatase calcineurin. While multiple distinct intracellular receptors for these drugs (cyclophilins and FKBPs, collectively immunophilins) have been characterized, the functionally active ones have not been discerned. We found that overexpression of cyclophilin A or B or FKBP12 increased T-cell sensitivity to CsA or FK506, respectively, demonstrating that they are able to mediate the inhibitory effects of their respective immunosuppressants in vivo. In contrast, cyclophilin C, FKBP13, and FKBP25 had no effect. Direct comparison of the Ki of each drug-immunophilin complex for calcineurin in vitro revealed that although calcineurin binding was clearly necessary, it was not sufficient to explain the in vivo activity of the immunophilin. Subcellular localization was shown also to play a role, since gene deletions of cyclophilins B and C which changed their intracellular locations altered their activities significantly. Cyclophilin B has been shown previously to be located within calcium-containing intracellular vesicles; its ability to mediate CsA inhibition implies that certain components of the signal transduction machinery are also spatially restricted within the cell.
Mol Cell Biol 1993 Aug
PMID:Identification of the immunophilins capable of mediating inhibition of signal transduction by cyclosporin A and FK506: roles of calcineurin binding and cellular location. 768 44

The particulate proteins of 34, 26, and 22 kDa are phosphorylated on serine residues in the rat parotid gland by activation of the cAMP-mediated signaling system. The 34 kDa protein was identified as ribosomal protein S6 by immunoprecipitation with anti S6 peptide antibody. The dephosphorylation of S6 was observed by incubation of the particulate fraction of the saponin-permeabilized cells labeled with [gamma-32P]ATP in the presence of cAMP/3-isobutyl-1-methylxanthine. The dephosphorylation of S6 was inhibited by either okadaic acid, a potent inhibitor of protein phosphatase, or Zn2+, however, neither Ca2+ nor Mg2+ showed significant effect. S6 phosphatase activities detected by using the 32P-labeled S6 peptide as a substrate were inhibited by both okadaic acid and Zn2+. These results suggest that the dephosphorylation of S6 is mediated by the okadaic acid and Zn(2+)-sensitive phosphatases in the rat parotid gland.
Biochem Mol Biol Int 1994 Dec
PMID:Dephosphorylation of ribosomal protein S6 phosphorylated via the cAMP-mediated signaling pathway in rat parotid gland: effect of okadaic acid and Zn2+. 769 90

To gain a better understanding of the relationship between the female rat reproductive system and preproenkephalin (PPE) expressing neurons under physiological conditions, we examined changes in PPE mRNA levels in the mediobasal hypothalamus during the rat estrous cycle by means of northern blotting and in situ hybridization histochemistry (ISHH). In the Northern blot studies, we found that PPE mRNA levels in the mediobasal hypothalamus were significantly increased by noon of proestrus compared to those in the morning and stayed high until diestrus day 1, and returned toward low levels on diestrous day 2. In contrast, measured as controls, glyceraldehyde-3-phosphate-dehydrogenase mRNA levels were significantly higher on proestrus regardless of time of day compared to diestrus day 2, and levels of calcineurin mRNA on proestrous and estrous were significantly lower than diestrous day 1 and day 2. ISHH studies revealed that these changes in PPE mRNA levels were specific in the ventromedial hypothalamic nucleus pars ventrolateralis (VMHVL), since we could not see any significant changes in signal in other parts including ventromedial hypothalamic nucleus pars dorsomedialis and arcuate hypothalamic nucleus. In the VMHVL, PPE mRNA levels in the afternoon of proestrous were significantly higher than those in the afternoon of diestrous day 2 whereas no significant change in PPE mRNA was observed in the caudate-putamen. The present study provides additional information relevant to possible implications of PPE gene expression in female reproductive systems, since changes in PPE mRNA levels may be associated with estrogen as well as progesterone or other hormonal concentrations during the estrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1995 Jan
PMID:Changes in preproenkephalin messenger RNA level in the rat ventromedial hypothalamus during the estrous cycle. 770 66

The expression of the two catalytic subunits of protein phosphatase (PP) type 1 PP1 gamma 1 and PP1 delta was examined in 4 cases of osteochondroma and 4 cases of enchondroma as a benign cartilaginous tumor, and 4 cases of chondrosarcoma as a malignant cartilaginous tumor using immunohistochemical analysis. The percentage of tumor cells stained positively with antiserum against PP1 catalytic subunit isoform PP1 gamma 1 were significantly higher in chondrosarcoma than in osteochondroma and enchondroma. Furthermore, chondrosarcoma showed markedly high S-phase fraction in the cell cycle of tumor cells, as compared to osteochondroma and enchondroma. These results suggest that PP1 gamma 1 is involved in the accelerated growth of malignant cells in chondrosarcoma.
Res Commun Mol Pathol Pharmacol 1994 Dec
PMID:Selective increase in expression of isoform PP1 gamma 1 of type-1 protein phosphatase in chondrosarcoma cells. 771 13

Tau is a neuron-specific, microtubule-associated protein that forms paired helical filaments (PHFs) of Alzheimer's disease when aberrantly phosphorylated. We have attempted to elucidate the protein kinases and phosphatases that regulate tau phosphorylation. Incubation of rat, human, and rhesus monkey temporal neocortex slices with the phosphatase inhibitor okadaic acid induced epitopes of tau similar to those found in PHFs. Okadaic acid (1-20 microM) induced variant forms of tau at 60-68 kDa, which were recognized by the monoclonal antibodies Alz-50 (in humans only) and 5E2 and two polyclonal antipeptide antisera, OK-1 and OK-2. The phosphorylation-sensitive monoclonal antibody Tau-1 failed to recognize the slowest mobility forms of tau after okadaic acid treatment. FK-520 (1-10 microM), a potent inhibitor of calcineurin activity, was tested in brain slices and found not to alter tau mobility. However, combinations of FK-520 (5 microM) and okadaic acid (100 nM) caused tau mobility shifts similar to those seen after 10 microM okadaic acid treatment; similar results were seen using the calcineurin-selective inhibitor cypermethrin. Treatment of human slices with 10 microM okadaic acid decreased both protein phosphatase 2A and calcineurin activity; FK-520 inhibited only protein phosphatase 2B activity. A proposed tau-directed kinase, 42-kDa mitogen-activated protein kinase (p42mapk), was activated by okadaic acid (> 100 nM) but not FK-520 (5 microM). Nerve growth factor (100 ng/ml) activated p42mapk, particularly when used in combination with 100 nM okadaic acid; changes in tau mobility were seen when this kinase was activated. Forskolin (2 microM) antagonized the effects of nerve growth factor on both p42mapk activity and tau phosphorylation; forskolin alone had little effect on PHF-like tau formation induced by phosphatase inhibitors. These results outline complex interactions between tau-directed protein kinases and protein phosphatases and suggest potential sites for therapeutic intervention.
Mol Pharmacol 1995 Apr
PMID:Tau phosphorylation in brain slices: pharmacological evidence for convergent effects of protein phosphatases on tau and mitogen-activated protein kinase. 772 35


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