Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphorylation of CTP synthetase (EC 6.3.4.2, UTP:ammonia ligase (ADP-forming)) from Saccharomyces cerevisiae protein kinase C was examined. Using pure CTP by synthetase as a substrate, protein kinase C activity was dose- and time-dependent and required calcium, diacylglycerol, and phosphatidylserine for full activation. Protein kinase C activity was also dependent on the concentration of CTP synthetase. Protein kinase C phosphorylated CTP synthetase on serine and threonine residues in vitro whereas the enzyme was primarily phosphorylated on serine residues in vivo. Phosphopeptide mapping analysis of CTP synthetase phosphorylated in vitro and in vivo indicated that the enzyme was phosphorylated on more than one site. Most of the phosphopeptides derived from CTP synthetase phosphorylated in vivo were the same as those derived from CTP synthetase phosphorylated by protein kinase C in vitro. The stoichiometry of the phosphorylation of native CTP synthetase was 0.4 mol of phosphate/mol of enzyme whereas the stoichiometry of the phosphorylation of alkaline phosphatase-treated CTP synthetase was 2.2 mol of phosphate/mol of enzyme. This indicated that CTP synthetase was purified in a phosphorylated state. Phosphorylation of CTP synthetase resulted in a 3-fold activation in enzyme activity whereas alkaline phosphatase treatment of CTP synthetase resulted in a 5-fold decrease in enzyme activity. Overall, the results reported here were consistent with the conclusion that CTP synthetase was regulated by protein kinase C phosphorylation.
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PMID:Phosphorylation of CTP synthetase from Saccharomyces cerevisiae by protein kinase C. 779 79

We have investigated a possible role for protein phosphorylation in nuclear transport in semi-intact cells, prepared by digitonin permeabilization of rat F-111 fibroblasts. Treatment of semi-intact cells with alkaline phosphatase abolished the import of nuclear transport substrates, namely, signal peptide-albumin conjugates, as well as their signal-dependent binding at the nuclear pores, but did not affect the morphology of the cells, in particular their cytoskeletal network. Authentic transport and functional binding of the karyophilic protein at the nuclear envelope could be restored by incubation of phosphatase-treated cells with cytosol enriched in protein kinase C or with purified protein kinase A (catalytic subunit). Restoration of transport was blocked by specific inhibitors of these kinases. Since the protein phosphorylation required for nuclear transport appeared to be a reasonably stable modification, characterization of the phosphorylated proteins was attempted in kinase reactions with radiolabeled ATP. Two proteins of 60-62 kDa were the predominant substrates phosphorylated by both protein kinase C and protein kinase A under conditions wherein nuclear transport was restored. Our results suggest a requirement for phosphorylation of one or more proteins for binding of a karyophilic protein at the nuclear envelope.
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PMID:Essential role of protein phosphorylation in nuclear transport. 781 12

Platelet actin binding protein (ABP) as isolated from human platelets exists in at least four phosphorylated forms which we have designated ABP-0, ABP-1, ABP-2, and ABP-3 whose phosphate content ranges from 18 (ABP-0) to 40 (ABP-3) moles Pi/mole ABP. These forms differ in their resistance to calpain cleavage and ability to cross-link F-actin with ABP-3 being the best in each of these properties. Attempts to phosphorylate ABP-1, two or three with protein kinase C (PKC) were unsuccessful except if the proteins were pretreated with Escherichia coli alkaline phosphatase. All of the forms could be phosphorylated with cAMP-dependent kinase (PKA) and subsequent resistance to calpain cleavage conferred. Phosphorylation/dephosphorylation of ABP may be an important regulatory mechanism by which the cytoskeletal architecture is stabilized or transformed.
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PMID:Existence of multiple phosphorylated forms of human platelet actin binding protein. 786 35

Phorbol-12-myristate-13-acetate (PMA) induced a dose-dependent proliferation of human hepatocarcinoma cell line SMMC-7721. In the presence of 100 nmol/L PMA, the activity of alkaline phosphatase was decreased and gamma-glutamyltransferase increased in the cell, suggesting that PMA is a proliferative inducer of hepatocarcinoma cell. PMA (100 nmol/L) also lead to a cytosol to membrane translocation of protein kinase C (PKC) within 5 minutes and down regulation after 1 hour. The decline of PKC activity in cytosolic fraction was far faster than that of membranous fraction. After long-term treatment with PMA for 1-5 days, the activities of PKC in cytosolic or membranous fraction almost disappeared, but the tyrosine protein kinase in both subcellular fractions was increased, being most obviously on the third day of culture. The increase in cytosolic TPK was more than that of membranous TPK, further indicating that TPK is a marker of cell proliferation.
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PMID:[Effect of phorbol ester on protein kinase C and tyrosine protein kinase in human hepatocarcinoma cell line]. 790 36

The effects of cAMP-dependent protein kinase A and protein kinase C on cell-cell communication have been examined in primary ovarian granulosa cells microinjected with purified components of these two regulatory cascades. These cells possess connexin43 (alpha 1)-type gap junctions, and are well-coupled electrotonically and as judged by the cell-to-cell transfer of fluorescent dye. Within 2-3 min after injection of the protein kinase A inhibitor (PKI) communication was sharply reduced or ceased, but resumed in about 3 min with the injection of the protein kinase A catalytic subunit. A similar resumption also occurred in PKI-injected cells after exposure to follicle stimulating hormone. Microinjection of the protein kinase C inhibitor protein caused a transient cessation of communication that spontaneously returned within 15-20 min. Treatment of cells with activators of protein kinase C, TPA or OAG for 60 min caused a significant reduction in communication that could be restored within 2-5 min by the subsequent injection of either the protein kinase C inhibitor or the protein kinase A catalytic subunit. With a longer exposure to either protein kinase C activator communication could not be restored and this appeared to be related to the absence of aggregates of connexin43 in membrane as detected immunologically. In cells injected with alkaline phosphatase communication stopped but returned either spontaneously within 20 min or within 2-3 min of injecting the cell with either the protein kinase A catalytic subunit or with protein kinase C. When untreated cells were injected with protein kinase C communication diminished or ceased within 5 min. Collectively these results demonstrate that cell-cell communication is regulated by both protein kinase A and C, but in a complex interrelated manner, quite likely by multiple phosphorylation of proteins within or regulating connexin-43 containing gap junctions.
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PMID:In situ regulation of cell-cell communication by the cAMP-dependent protein kinase and protein kinase C. 793 58

The effects of some protein kinase effectors on phosphohydrolase and transport activities of yeast vacuoles have been studied. The platelet-activating factor (PAF), a plant vacuolar protein kinase C stimulator, had a protonophoric and membrane-damaging effects on yeast vacuoles and inhibited the ATP-dependent delta mu H+ formation and ATP-dependent secondary transport but stimulated the ATPase and pyrophosphatase hydrolase activities by abrogating proton control. PAF increasing the tonoplast permeability for the corresponding substrates also stimulated pyrophosphatase, polyphosphatase and alkaline phosphatase activities. Lysolipid sphingosine, a plant vacuolar protein kinase C inhibitor, poorly stimulated the ATPase activity and the ATP-dependent formation of Em in isolated yeast vacuoles, while the pyrophosphatase activity increased by 200%. Other hydrolase activities tested were insensitive to the effect of the lysolipid. Sphingosine inhibited the ATP-dependent citrate transport only insignificantly. Heparin, an effective casein kinase inhibitor, suppressed the ATPase and polyphosphatase activities in isolated yeast vacuoles. The polyphosphatase activity was inhibited both in the vacuolar sap and the tonoplast solubilized by a Zwittergent TM-314, in contrast with the ATPase activity which was inhibited by heparin only in isolated vacuoles. Heparin is suggested to inhibit polyphosphatase by directly influencing the enzyme.
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PMID:[The effect of PAF, sphingosine and heparin on certain phosphohydrolase and transport activity of yeast vacuoles]. 794 17

We previously reported that fetal calf serum-induced alkaline phosphatase activity is suppressed due to the activation of protein kinase C in osteoblast-like MC3T3-E1 cells (Miwa et al. (1991) Bone Miner. 14, 15-25; Kotoyori et al. (1994) Horm. Metab. Res. 26, 116-118). In the present study, we examined the effect of okadaic acid, a potent and specific inhibitor of protein phosphatase type 1 and 2A, on fetal calf serum-induced alkaline phosphatase activity in MC3T3-E1 cells. The pretreatment with okadaic acid enhanced the fetal calf serum-induced alkaline phosphatase activity in a dose-dependent manner in the range between 0.1 and 5 nM. 1-Norokadaone, a less potent analogue of okadaic acid, had little effect on the fetal calf serum-induced alkaline phosphatase activity. Okadaic acid partially reversed the suppression of fetal calf serum-induced alkaline phosphatase activity by 12-O-tetradecanoylphorbol-13-acetate, a protein kinase C activator. The effect of okadaic acid was dose-dependent in the range between 0.1 and 5 nM. The patterns of the dose-dependency of both okadaic acid effects on fetal calf serum-induced alkaline phosphatase activity and on the suppression by 12-O-tetradecanoylphorbol-13-acetate were similar. These results strongly suggest that protein phosphatase type 1 and/or 2A act as a regulator of alkaline phosphatase activity at a point downstream from protein kinase C in osteoblast-like cells.
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PMID:Okadaic acid reverses the inhibitory effect of protein kinase C on alkaline phosphatase activity in osteoblast-like cells. 795 88

Caveolae are specialized invaginations of the plasma membrane which have been proposed to play a role in diverse cellular processes such as endocytosis and signal transduction. We have developed an assay to determine the fraction of internal versus plasma membrane caveolae. The GPI-anchored protein, alkaline phosphatase, was clustered in caveolae after antibody-induced crosslinking at low temperature and then, after various treatments, the relative amount of alkaline phosphatase on the cell surface was determined. Using this assay we were able to show a time- and temperature-dependent decrease in cell-surface alkaline phosphatase activity which was dependent on antibody-induced clustering. The decrease in cell surface alkaline phosphatase activity was greatly accelerated by the phosphatase inhibitor, okadaic acid, but not by a protein kinase C activator. Internalization of clustered alkaline phosphatase in the presence or absence of okadaic acid was blocked by cytochalasin D and by the kinase inhibitor staurosporine. Electron microscopy confirmed that okadaic acid induced removal of caveolae from the cell surface. In the presence of hypertonic medium this was followed by the redistribution of groups of caveolae to the center of the cell close to the microtubule-organizing center. This process was reversible, blocked by cytochalasin D, and the centralization of the caveolar clusters was shown to be dependent on an intact microtubule network. Although the exact mechanism of internalization remains unknown, the results show that caveolae are dynamic structures which can be internalized into the cell. This process may be regulated by kinase activity and require an intact actin network.
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PMID:Regulated internalization of caveolae. 796 85

The present study was performed to clarify second messenger signaling in parathyroid hormone (PTH)-induced c-fos gene expression, to characterize the participation of the c-fos gene in the regulation of osteoblast proliferation and function as well as osteoclast-like cell formation by PTH and to compare these effects of PTH with those of PTH-related peptide (PTHrP). Both human (h) PTH-(1-34) and hPTHrP-(1-34) at 10(-8) M induced a transient c-fos gene expression to a similar degree in osteoblastic osteosarcoma cells, UMR-106. N6,O2'-dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) as well as Sp-diastereoisomer of adenosine cyclic 3',5'-phosphorothioate (Sp-cAMPS), an activator of cAMP-dependent protein kinase (PKA), induced a weak c-fos gene expression. Although Rp-diastereoisomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS), an inhibitor of PKA, almost completely antagonized dbCAMP- and Sp-cAMPS-induced expression of c-fos gene, it did not cause an obvious inhibition of PTH- or PTHrP-induced expression. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), induced an intense expression of the c-fos gene, while 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD), incapable of activating PKC, and calcium ionophores (A23187 and ionomycin) did not. Protein kinase C inhibitor (H-7, 50 microM) completely blocked the expression of the c-fos gene by PTH as well as by PTHrP). Antisense oligodeoxynucleotides (as-ODN) complementary to c-fos mRNA, which have been shown to inhibit its mRNA translation, at 1 microM significantly antagonized PTH- and PTHrP-induced inhibition of [3H] thymidine incorporation and stimulation of osteoclast-like cell formation in the presence of osteoblasts, but not an increase in alkaline phosphatase activity, compared to control oligodeoxynucleotides with same nucleotides as as-ODN but with a random sequence. The present study indicates the involvement of PKC system in c-fos gene expression by PTH as well as PTHrP and also indicates the involvement of the c-fos gene in the regulation of bone cell physiology by PTH and PTHrP.
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PMID:Second messenger signaling of c-fos gene induction by parathyroid hormone (PTH) and PTH-related peptide in osteoblastic osteosarcoma cells: its role in osteoblast proliferation and osteoclast-like cell formation. 796 20

Parathyroid hormone (PTH) plays a central role in regulation of calcium metabolism. For example, excessive or inappropriate production of PTH or the related hormone, parathyroid hormone related protein (PTHrP), accounts for the majority of the causes of hypercalcemia. Both hormones act through the same receptor on the osteoblast to elicit enhanced bone resorption by the osteoclast. Thus, the osteoblast mediates the effect of PTH in the resorption process. In this process, PTH causes a change in the function and phenotype of the osteoblast from a cell involved in bone formation to one directing the process of bone resorption. In response to PTH, the osteoblast decreases collagen, alkaline phosphatase, and osteopontin expression and increases production of osteocalcin, cytokines, and neutral proteases. Many of these changes have been shown to be due to effects on mRNA abundance through either transcriptional or post-transcriptional mechanisms. However, the signal transduction pathway for the hormone to cause these changes is not completely elucidated in any case. Binding of PTH and PTHrP to their common receptor has been shown to result in activation of protein kinases A and C and increases in intracellular calcium. The latter has not been implicated in any changes in mRNA of osteoblastic genes. On the other hand activation of PKA can mimic all the effects of PTH; protein kinase C may be involved in some responses. We will discuss possible mechanisms linking PKA and PKC activation to changes in gene expression, particularly at the nuclear level.
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PMID:Signal transduction pathways mediating parathyroid hormone regulation of osteoblastic gene expression. 796 63


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