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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)

The mechanism of placental alkaline phosphatase (PLAP) induction by prednisolone in a uterine cervical epidermoid cancer cell line SKG-IIIa was investigated in vitro by enzyme-cytochemistry, enzyme immunoassay, Northern and Southern blot analysis, and in situ hybridization. Enzyme-cytochemical alkaline phosphatase (ALP) staining and immunoassay revealed increased levels of PLAP (heat-stable ALP) in prednisolone-treated cells. Northern blot analysis and in situ hybridization showed increased amounts of PLAP mRNA. Southern blot analysis indicated that PLAP was not a product of an amplified or rearranged gene. These findings suggest that the induction of PLAP mRNA in SKG-IIIa cells by prednisolone in turn increased the levels of PLAP.
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PMID:The mechanism of placental alkaline phosphatase induction in vitro. 267 29

Electrophoretic patterns of seminoma- and normal-testis-derived alkaline phosphatase isozymes, the placental alkaline phosphatase (PLAP)-like enzyme and the tissue-nonspecific (liver) alkaline phosphatase (LAP), were studied on starch gel and isoelectric focusing (IEF). Different migration patterns of the PLAP-like enzyme were observed with respect to both seminomas and normal testes on starch gel electrophoresis. On IEF, seminomas showed different staining patterns among different tumors; however, a common main activity was focused at pIs of 4.3-4.6, corresponding to pIs of PLAP. Normal testes showed two enzyme-staining regions, at pIs of 4.1 and 5.0-5.2, which were discriminated from pIs of PLAP and the PLAP-like enzyme in seminoma. The PLAP-like enzyme in seminoma was differentiated from PLAP by digestion with neuraminidase. Neuraminidase treatment simplified the distribution patterns of the PLAP-like enzyme in normal testis, but did not alter the pattern of microheterogeneity in seminoma. Two factors other than sialylation, namely structural modification of the carbohydrate moiety and variation of hydrophobicity, were shown to contribute to the microheterogeneity of the PLAP-like enzyme in seminoma. LAP in seminoma and in normal testis also showed marked electrophoretic heterogeneity and differences in pI distributions from LAP of liver. However, the migration patterns after desialylation were very similar to each other. The findings imply that electrophoretic heterogeneity demonstrated in LAP in seminoma and in normal testis is caused by a difference in sialic acid content in the molecule, and the heterogeneity of the PLAP-like enzyme in seminoma is considerable.
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PMID:Electrophoretic heterogeneity of alkaline phosphatase isozymes in seminoma and normal testis. 278 Dec 21

LoVo, a continuous cell line derived from a human colon carcinoma produces two alkaline phosphatases: the heat-labile, L-homoarginine-insensitive, intestinal form, characteristic of its tissue of origin and the heat-stable, term-placental form, ectopically produced by a variety of tumors. Under basal conditions the activity levels of both enzymes are similar. Hyperosmolality and sodium butyrate induce increased levels of activity of the two alkaline phosphatases in a disparate fashion; whereas hyperosmolality augments the activity of both to the same extent, the effect of butyrate is more pronounced on the activity of the intestinal enzyme. When the two inducers are combined, induction of term-placental alkaline phosphatase is additive and that of the intestinal enzyme is synergistic. The effect of hyperosmolality is blocked by cycloheximide, and induction by sodium butyrate is inhibited by thymidine, cordycepin and cycloheximide. The known alkaline phosphatase inducer, prednisolone, has no effect on the enzymes of LoVo cells. Our results suggest that in these tumor cells the activity levels of the closely homologous term-placental and intestinal alkaline phosphatases appear to be independently controlled.
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PMID:Modulation of alkaline phosphatases in LoVo, a human colon carcinoma cell line. 280 87

Placental alkaline phosphatase [orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] is a member of a diverse group of membrane proteins whose attachment to the lipid bilayer is mediated by a phosphatidylinositol-glycan. To investigate structural aspects of the glycolipid anchor, cultured WISH cells were used because we found that they produce the enzyme in abundant quantities. When cell suspensions were incubated with purified phosphatidylinositol-specific phospholipase C, most of the placental alkaline phosphatase was released from membranes in a hydrophilic form. On incubation of the cells with [14C]ethanolamine, [14C]myristic acid, or myo-[3H]inositol, each was incorporated into the phosphatase near the carboxyl terminus, showing that these components, which are found in other phosphatidylinositol membrane-linked proteins, are also present in placental alkaline phosphatase.
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PMID:Characterization of the phosphatidylinositol-glycan membrane anchor of human placental alkaline phosphatase. 281 64

Alkaline phosphatase is anchored to the plasma membrane by a carboxyl-terminal phosphatidylinositol glycan moiety. To investigate the biosynthesis of mature alkaline phosphatase, nascent human placental alkaline phosphatase was expressed in a cell-free system and used as substrate for in vitro processing by microsomal extracts. By monitoring the processed product with three site-directed antibodies, it was shown that microsomal extracts from CHO cells that contain other recognized processing activities also remove the carboxyl-terminal signal peptide from the preproenzyme in an apparently selective manner. This peptidase-like cleavage may be brought about by the action of a specific transamidase acting on the nascent protein in the absence of an appropriate phosphatidylinositol glycan cosubstrate.
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PMID:Processing at the carboxyl terminus of nascent placental alkaline phosphatase in a cell-free system: evidence for specific cleavage of a signal peptide. 291 71

A human term (third trimester) placental alkaline phosphatase (PLAP; EC 3.1.3.1) cDNA was isolated from a human placental lambda gt11 cDNA library. The expression library was screened by using rabbit antibodies against PLAP and oligonucleotide probes. DNA sequence analysis of a positive clone with an insert of 2.7 kilobase pairs allowed us to predict the complete amino acid sequence of PLAP (530 residues), which coincided with the reported 42 N-terminal amino acid sequence of PLAP except at position 3. Contrary to the previous supposition that there was no amino acid sequence homology between PLAP and Escherichia coli alkaline phosphatase (471 residues), we found 30% overall homology, with regions of strong homology including the putative active site and the metal-binding sites. The 44-residue C-terminal extension of PLAP has a stretch of 17 hydrophobic amino acids, which presumably anchors the protein to the plasma membrane, a change perhaps necessary for the transition from a bacterial periplasmic enzyme to a mammalian membrane-associated enzyme. We have also localized PLAP-related DNA sequences mainly on chromosome 2 and to a lesser degree on chromosome 17. It seems likely therefore that the PLAP gene resides on chromosome 2 and other member(s) of the alkaline phosphatase family may exist (on this chromosome and) on chromosome 17.
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PMID:Cloning, sequencing, and chromosomal localization of human term placental alkaline phosphatase cDNA. 300 17

A specific radioimmunoassay for human placental alkaline phosphatase has been developed using the 125I-labeled enzyme, highly purified with a fast protein liquid chromatography system and an absorbed rabbit antiserum. The sensitivity of this assay was 0.2 U/L. Serum levels of over 0.2 U/L were found in 27% of ovarian cancer patients, and most of these elevated enzyme levels occurred with more advanced stages of the disease. On the other hand, almost all ovarian cancer tissue contained detectable levels of the enzyme. Serous adenocarcinoma, endometrioid adenocarcinoma, and dysgerminoma had particularly large amounts. Placental alkaline phosphatase was more frequently detected in tissue than in the serum of ovarian cancer, and therefore may be a useful target in immunodetection and immunotherapy and in studying the histopathology of ovarian cancer.
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PMID:Radioimmunoassay of placental alkaline phosphatase in ovarian cancer sera and tissues. 302 85

Three closely related alkaline phosphatase (ALP) genes reside on the long arm of chromosome 2 in man. One of these genes (the placental ALP-1) encodes the classic heat-stable placental alkaline phosphatase. Another gene (the placental ALP-2) is closely related to the placental ALP-1 and may encode the so-called placental ALP-like enzyme of the testis and thymus. The third member of this gene family (the intestinal ALP gene) encodes the intestinal alkaline phosphatase. The expression of the placental ALP-1 and intestinal ALP genes is highly tissue-specific in spite of nearly 90% sequence similarity within their exons. To help determine the basis for this tissue specificity, the nucleotide sequence of the placental ALP-1 gene and some of its 5' flanking region has been determined and analyzed by comparison with placental ALP-2 and intestinal ALP gene sequences. The placental ALP-1 gene transcription unit has 4087 bases between the major cap site and the most distal of several reported 3' ends. The protein coding region is divided by 10 short introns varying in size from 74 to 241 nucleotides. Three of these introns bisect regions of the gene that encode residues conserved between the active site of the Escherichia coli enzyme and the human placental ALP. This result suggests that the human alkaline phosphatase genes have evolved in an intron-independent fashion. A comparison of the placental ALP-1 5' flanking sequence (up to -540) with the analogous sequence of the intestinal ALP gene revealed several deletion/substitutions which could be important in determining the tissue-specific expression of these genes.
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PMID:Nucleotide sequence of the human placental alkaline phosphatase gene. Evolution of the 5' flanking region by deletion/substitution. 304 87

The gene encoding the mouse placental alkaline phosphatase (ALP; orthophosphoric-monoester phosphohydrolase, alkaline optimum, EC 3.1.3.1) is mapped to chromosome 4, based on Southern blot hybridization of the mouse cDNA with DNAs from mouse-Chinese hamster somatic cell hybrids. This assignment is consistent with the genetic analysis of the Akp-2 locus, which is responsible for the genetic variation of alkaline phosphatase enzyme in placenta as well as in liver, kidney, and bone.
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PMID:Mapping of gene encoding mouse placental alkaline phosphatase to chromosome 4. 316 38

In man, there are multiple forms of alkaline phosphatase encoded by at least three homologous genes: placental, intestinal, and liver/bone/kidney. This report describes the characterization of the human liver/bone/kidney alkaline phosphatase locus. The gene appears to exist as a single copy in the haploid genome and is comprised of 12 exons distributed over more than 50 kilobases. In liver, kidney, SAOS-2 human osteosarcoma cells, and cultured fibroblasts, there is a single major start for transcription situated about 25 nucleotides downstream of an A/T-rich motif. The promoter region is extremely G/C-rich, is relatively abundant in the dinucleotide CpG, and contains four copies of the consensus sequence for SP1 binding (GGGCGG). The liver/bone/kidney alkaline phosphatase gene is at least five times larger than the intestinal and placental alkaline phosphatase genes, mainly due to intron size differences. Intron-exon junctions occur at analogous positions in all three genes, but there is an extra non-coding exon at the 5' end of the liver/bone/kidney alkaline phosphatase gene. The relevance of our findings with respect to the evolution of the human alkaline phosphatase multigene family is discussed.
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PMID:Structure of the human liver/bone/kidney alkaline phosphatase gene. 316 80


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