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)

A human osteosarcoma cell line, HuO9, was established from a tumor that was heterotransplanted into athymic nude mice. Antiserum against nude mouse spleen cells was added to the early passage cultures to eliminate the host fibroblastic cells. The cell line retained a high activity of liver/bone/kidney-type alkaline phosphatase (ALP) and secreted osteocalcin, i.e., bone gamma-carboxyglutamic acid-containing protein (BGP), into the medium. The addition of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) increased the ALP activity as well as the level of BGP secreted into the medium. The ALP of 1,25(OH)2D3-treated cells has the same inhibition characteristics to heat and amino acids as that of untreated cells. Synthetic human parathyroid hormone stimulated the production of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) approximately 100-fold within five minutes. However, the stimulation was not observed with a synthetic human thyrocalcitonin. When HuO9 cells were transplanted into the back of a nude mouse, a tumor with an abundant osteoid formation and mineralization was produced. The results indicate that the HuO9 cell line expresses well-differentiated osteoblastic phenotypes. HuO9 is the first established human cell line to produce BGP, and it provides a useful model for the studies of osteoblasts and the regulatory mechanisms of BGP production.
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PMID:A newly established human osteosarcoma cell line with osteoblastic properties. 217 70

The gene coding for the mouse alkaline phosphatase expressed in liver, bone, kidney and placenta (liver/bone/kidney-type alkaline phosphatase, L/B/K-ALP) was isolated and characterized. This gene consists of 12 exons and it is at least 49 kb long. The first two exons are separated by a long intron which is at least 32 kb in size, whereas the other exons span within the remaining 17 kb. Primer extension and S1-nuclease mapping analyses with placental mRNA demonstrate a single major transcription start site, which is preceded by a G + C-rich region containing a TATA-like sequence and three copies of the consensus binding site for the transcription factor Sp1. Transfection experiments using two different reporter genes show that the 5'-flanking region of the gene is active as a promoter in undifferentiated F9 teratocarcinoma cells, but not in 3T3 fibroblasts, consistent with the L/B/K-ALP mRNA level in the two cell lines. As expected from the sequence similarity at the cDNA level, the structural organization of the mouse gene is similar to that of the human and rat L/B/K-ALP genes, suggesting that they all derive from a single ancestral gene.
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PMID:Isolation and characterization of the mouse liver/bone/kidney-type alkaline phosphatase gene. 236 2

The gene coding for the liver/bone/kidney isozyme of alkaline phosphatase, ALPL, has been mapped to human chromosome 1 using a monoclonal antibody TRA-2-54/2J and electrophoretic analysis to distinguish between the human and rodent isozymes in human/rodent somatic cell hybrids.
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PMID:Mapping of the gene coding for the human liver/bone/kidney isozyme of alkaline phosphatase to chromosome 1. 344 11

From a series of hybridomas that produced monoclonal antibodies reactive with the surface of human embryonal carcinoma cells, two that specifically recognized determinants of the liver/bone/kidney isozyme of alkaline phosphatase were isolated. They did not cross-react with the intestinal or placental isozymes. Phylogenetic studies revealed that both antibodies cross-reacted strongly with liver alkaline phosphatase from higher primates, but exhibited marked differences in their respective cross-reactions with liver alkaline phosphatase from other mammalian species.
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PMID:Two monoclonal antibodies recognizing determinants on human embryonal carcinoma cells react specifically with the liver isozyme of human alkaline phosphatase. 620 84

Tissue-nonspecific-type alkaline phosphatase is found in the bone, liver, kidney, and other tissues, and its gene consists of 12 exons with the coding sequence beginning in the second exon. Recently, an alternative noncoding first exon was identified in the liver message which differed from that of the previously known osteoblast-derived cDNA sequence. Although these two mRNAs produce an identical protein, they have different promoter regions. The periodontal ligament tissue expresses a high level of alkaline phosphatase activity. To identify its mRNA type, we isolated a full-length cDNA for alkaline phosphatase from a cultured human periodontal ligament cell expression library, using bone-derived tissue-nonspecific alkaline phosphatase cDNA as a hybridization probe. The size of this clone was 2.5 kb, and its 5' and 3' untranslated sequences were identical to those of the human tissue-nonspecific type isolated from osteoblastic cells but not to those of the liver type. In addition, the same fragments as in bone-derived tissue-nonspecific-type cDNA were detected by the treatment of the cDNA clone with restriction enzymes Hinc II and Pst I. The results suggest that expression of the same alkaline phosphatase isozyme in human periodontal ligament cells may be regulated by the same transcriptional mechanism as in bone.
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PMID:Identification of bone-type alkaline phosphatase mRNA from human periodontal ligament cells. 787 24

Alkaline phosphatase activity is present in the mesoderm of embryonic chick skin and becomes spatially restricted to the dermal condensation of the developing feather germs. Inhibitors to tissue-nonspecific (liver/bone/kidney), but not intestinal alkaline phosphatase inhibit the establishment and growth of feather germs in cultured skins. A window of maximum sensitivity to the inhibitor was observed to be the first day of culture when early development and establishment of pattern takes place. The cDNA for the avian tissue-nonspecific alkaline phosphatase was cloned and sequenced, and Southern analysis revealed a single copy of this gene in the avian genome. Northern analysis revealed that a 2.8 kb transcript for this form of alkaline phosphatase is present in developing skin.
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PMID:Tissue-nonspecific alkaline phosphatase participates in the establishment and growth of feather germs in embryonic chick skin cultures. 856 25

Hypophosphatasia is associated with a defect of the tissue-non-specific alkaline phosphatase gene. We performed a mutational analysis in a surviving patient diagnosed at birth as having hypophosphatasia, on the basis of a low level of serum alkaline phosphatase (ALP) activity and characteristic radiographical findings. She had two sisters, one of whom died of respiratory failure complicated by perinatal hypophosphatasia; the other seemed healthy, with a relatively low activity level of ALP. The patient's parents also had low ALP activity. Sequence analysis of the tissue-nonspecific alkaline phosphatase gene was performed, using genomic DNA and total RNA from the skin fibroblasts of the patient and the peripheral mononuclear cells of her parents. The conversion of Phe to Leu at codon 310 (F310L) and Gly to Arg at 439 (G439R) were identified in the patient. Interestingly, the reconstructive experiments demonstrated that the F310L mutant exhibited an ALP activity level 65% of the normal level, whereas the mutant G439R had no activity. Moreover, the digestion by StuI, after a PCR using complementary DNA extracted from fibroblasts of the patient and lymphocytes of her father, revealed a relatively low messenger RNA level of F310L. These findings suggest that the neonatal case of hypophosphatasia was associated with compound mutations, one of which caused the loss of ALP activity and the other of which caused a slight reduction of the ALP activity, with a relatively low level of messenger RNA.
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PMID:Identification of novel missense mutations (Phe310Leu and Gly439Arg) in a neonatal case of hypophosphatasia. 895 59

Leukocyte alkaline phosphatase (LAP) is the product of the gene coding for the liver/bone/kidney-type alkaline phosphatase. In the normal hematopoietic system, the only cell type expressing LAP in basal conditions is the post-mitotic neutrophilic granulocyte. Thus LAP represents a specific and restrictive marker for the terminal maturation of the neutrophilic granulocyte. The study of the factors and the molecular mechanisms responsible for the expression of LAP in cells undergoing granulocytic maturation may shed light on this complex biological process. Acute promyelocytic leukemia (APL) represents a unique biological model in which it is possible to investigate neutrophilic differentiation. APL blasts undergo rapid and irreversible maturation towards cells morphologically and biochemically resembling normal mature granulocytes upon in vivo and in vitro challenge with all-trans retinoic acid (ATRA). In this cellular context, we studied the endogenous factors involved in the expression of LAP. The phosphatase is not synthesized in undifferentiated APL blasts and it is expressed only upon treatment with combinations between ATRA and a second cyto-differentiating signal. The second signal may be given by G-CSF, cAMP analogs, IL-6 and to a lesser extent by IL-1 beta. The molecular mechanisms underlying the induction of LAP by combinations of ATRA and G-CSF or cAMP analogs were studied in detail and are the object of this review.
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PMID:Leukocyte alkaline phosphatase a specific marker for the post-mitotic neutrophilic granulocyte: regulation in acute promyelocytic leukemia. 903 Oct 80

We have studied the biosynthesis and intracellular transport of tissue-nonspecific alkaline phosphatase (TNSALP) transiently expressed in COS-1 cells. Mutations were introduced into TNSALP to examine the effects of a single amino acid substitution on the activity and biosynthesis of TNSALP. The cells expressing wild-type TNSALP exhibited more than 200-fold higher alkaline phosphatase activity than untransfected ones. Pulse-chase experiments showed that TNSALP was synthesized as a 66-kDa endoglucosaminidase H (Endo H)-sensitive form and converted to EndoH-resistant forms with heterogenous molecular masses ( approximately 80 kDa), which finally appeared on the cell surface as judged by digestion with phosphatidylinositol-specific phospholipase C (PI-PLC). In contrast, a TNSALP with a Glu218-->Gly mutation exhibited no phosphatase activity at all and the 66-kDa Endo H-sensitive form was the only molecular species throughout the chase in the transfected cells. In accordance with this finding, digestion with PI-PLC and immunofluorescence observation confirmed that this mutant was never expressed on the cell surface. Another mutant with a Ala162-->Thr substitution, which naturally occurs in association with a lethal hypophosphatasia, exhibited a low activity and only a small fraction of the 66-kDa form acquired Endo-H resistance and reached the cell surface. Since the wild-type and the mutant TNSALPs were labeled with [3H]ethanolamine, a component of glycosylphosphatidylinositol (GPI), it is unlikely that the impaired intracellular transport of the two mutants is due to a failure in their modification by GPI. Interestingly, the 66-kDa Endo H-sensitive form of the TNSALP mutants but not that of the wild-type, was found to form an interchain disulfide-bonded high-molecular-mass aggregate within the cells. These results suggest that impaired intracellular transport of the TNSALP (Ala162-->Thr) molecule caused by its aggregation is the molecular basis for the lethal hypophosphatasia carrying this mutation.
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PMID:Defective intracellular transport of tissue-nonspecific alkaline phosphatase with an Ala162-->Thr mutation associated with lethal hypophosphatasia. 956 33

One point mutation which converts glycine-317 to aspartate of tissue-nonspecific alkaline phosphatase (TNSALP) was reported to be associated with lethal hypophosphatasia (Greenberg, C. R., et al. Genomics 17, 215-217, 1993). In order to define the molecular defect of TNSALP underlying the pathogenesis of hypophosphatasia, we have examined the biosynthesis of TNSALP with a Gly317-->Asp substitution. When expressed in COS-1 cells, the mutant did not exhibit alkaline phosphatase activity at all, indicating that the replacement of glycine-317 with aspartate abolishes the catalytic activity of TNSALP. Pulse-chase experiments showed that the newly synthesized mutant failed to acquire Endo H-resistance and to reach the cell surface. Interestingly, this TNSALP mutant was found to form a disulfide-bonded high-molecular-mass aggregate and was rapidly degraded within the cell, though the mutant protein was modified by glycosylphosphatidylinositol (GPI). Lactacystin, an inhibitor of the proteasome, obstructed the degradation of the mutant protein, suggesting the involvement of proteasome as a part of quality control of TNSALP.
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PMID:Intracellular retention and degradation of tissue-nonspecific alkaline phosphatase with a Gly317-->Asp substitution associated with lethal hypophosphatasia. 961 60


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