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

---

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

Nascent precursors of phosphatidylinositol-glycan (PI-G)-linked membrane proteins contain a hydrophobic COOH-terminal sequence of 15-30 residues that is eliminated during processing to yield a newly exposed COOH terminus to which the PI-G moiety is added. There is no consensus as to the primary structure of the terminal peptide but there is a specific requirement for the amino acid destined to become the COOH terminus. In nascent human placental alkaline phosphatase (PLAP), the PI-G tail is attached to Asp-484. Site-directed mutants with glycine, alanine, cysteine, serine, or asparagine (category I) at residue 484 become PI-G tailed, appear in the plasma membrane, and are enzymatically active when expressed in COS cells. Although mutants with glutamic acid, glutamine, proline, tryptophan, leucine, valine, phenylalanine, threonine, methionine, and tyrosine (category II) are expressed equally well, only small amounts appear on the plasma membrane. Furthermore, they are not PI-G tailed and have little alkaline phosphatase activity. Studies with truncated PLAP-489 rule out nonspecific conformational changes in category II mutant proteins as a reason for their failure to be processed in COS cells and point to a specific COOH-terminal processing enzyme. Direct evidence that the selectivity for category I amino acids is enzymatically determined was obtained in a cell-free translation/processing system by using rabbit reticulocyte lysate and CHO cell rough microsomal membranes. In this in vitro system, both category I and category II mutants of PLAP-513 were translated, glycosylated, and cleaved by NH2-terminal signal peptidase. However, an additional and selective cleavage at residue 484 was observed only with category I mutants.
...
PMID:Selectivity at the cleavage/attachment site of phosphatidylinositol-glycan anchored membrane proteins is enzymatically determined. 170 Apr 20

The role of serum alkaline phosphatase as a tumor marker for testicular germ cell disease was investigated in 26 patients with testicular seminoma and 13 with nonseminomatous germ cell testis tumors. Placental alkaline phosphatase-like enzyme was elevated in 50% of the stage I seminoma patients and in all patients with stages II to III disease. In addition, liver (tissue unspecific) alkaline phosphatase was elevated in 10 and 83% of the patients, respectively. Lactic dehydrogenase and beta-human chorionic gonadotropin (beta-HCG) were detected in 50 to 60% of the patients with stage I seminoma. By combining placental alkaline phosphatase-like enzyme, lactic dehydrogenase and beta-HCG, 75% of the stage I and 100% of the stages II and III seminoma patients could be identified correctly. Placental alkaline phosphatase-like enzyme in serum also occurred with nonseminomatous germ cell tumor but less frequently, while liver alkaline phosphatase was not detected at all. Thus, placental alkaline phosphatase-like enzyme and liver alkaline phosphatase were predominantly determined in the serum of patients with seminoma. In studies of tumor tissues from 31 of these patients, those with normal serum placental alkaline phosphatase-like enzyme levels had significantly lower tissue placental alkaline phosphatase-like enzyme levels than patients with elevated serum levels (p less than 0.01). Seminoma tissues showed significantly higher levels of placental alkaline phosphatase-like enzyme and liver alkaline phosphatase than nonseminomatous germ cell tumors (p less than 0.01), explaining the infrequent elevation of serum placental alkaline phosphatase-like enzyme and liver alkaline phosphatase found in patients with nonseminomatous germ cell tumors.
...
PMID:The role of alkaline phosphatase isoenzymes as tumor markers for testicular germ cell tumors. 171 86

Observations differ on the pre-invasive malignant lesions associated with the various categories of testicular germ cell tumours. Such lesions have been found to be similar in appearance and are assumed to be composed of multipotent cells, or conversely a distinctive pre-invasive stage has been reported in association with each form of germ cell neoplasm. This study was undertaken to see whether distinctive morphological and immunohistochemical features of carcinoma in situ adjacent to various categories of germ cell tumours could be established. Carcinoma in situ adjacent to seminomas, teratomas and mixed germ cell tumours in 18 adults was indistinguishable morphologically. Placental alkaline phosphatase was demonstrated immunohistochemically but vimentin and low molecular weight cytokeratins were uniformly absent in these abnormal germ cells from all three groups. These findings support the concept of a multipotent pre-invasive malignant cell for both seminoma and teratoma in the adult. Carcinoma in situ was not seen adjacent to 15 spermatocytic seminomas, nor was placental alkaline phosphatase demonstrated in tubules adjacent to these tumours. These negative findings are additional evidence that spermatocytic seminoma differs from classical seminoma in its histogenesis. Carcinoma in situ, as defined morphologically and immunohistochemically in adults, was not identified adjacent to yolk sac tumours and differentiated teratomas in 20 prepubertal testes. The possibility that pre-invasive malignancy in children may not resemble that in adults must be considered when assessing the malignant potential of cryptorchid testes on biopsies taken during orchidopexy.
...
PMID:Morphology and immunohistochemistry of carcinoma in situ adjacent to testicular germ cell tumours in adults and children: implications for histogenesis. 172 58

We have developed hybridization probes that clearly distinguish the RNA transcripts of the two closely related human heat-stable alkaline phosphatase genes. RNA from the PLAP-1 gene, encoding the term placental alkaline phosphatase, is the predominant transcript in placenta from 8 weeks to term. Transcripts from the PLAP-2 gene, encoding the germ-cell or PLAP-like enzyme, are also detectable in the placenta, but at no more than 2 per cent the level of PLAP-1 transcripts.
...
PMID:Trace expression of the germ-cell alkaline phosphatase gene in human placenta. 172 15

Amphiphilic and hydrophilic forms of alkaline phosphatase differed in electrophoretic mobility, sensitivity to heat, activation by phospholipids and albumin, and affinity of monoclonal antibodies, but were similar in substrate Km and inhibitor Ki values, sensitivity to sodium dodecyl sulfate, and electrophoretic behavior on desialylation. Chemical cross-linking experiments failed to conclusively demonstrate an aggregated state of amphiphilic alkaline phosphatase in Triton X-100. Further, attempts to identify a polymeric hybrid between amphiphilic forms of human liver and placental alkaline phosphatase were unsuccessful. We conclude that the covalent attachment of the hydrophobic phosphatidyl-inositol membrane anchor causes the amphiphilic form to behave anomalously on electrophoresis and to affect certain of the enzyme's catalytic and physical properties.
...
PMID:Properties of amphiphilic and hydrophilic forms of alkaline phosphatase from human liver. 181 49

Mammalian serum and plasma contain high levels of glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD). Previous studies with crude serum or partially purified GPI-PLD have shown that this enzyme is capable of degrading the GPI anchor of several purified detergent-solubilized cell surface proteins yet is unable to act on GPI-anchored proteins located in intact cells. Treatment of intact ROS17/2.8, WISH or HeLa cells (or membrane fractions prepared from them) with GPI-PLD purified from bovine serum by immunoaffinity chromatography gave no detectable release of alkaline phosphatase into the medium. However, when membranes were treated with GPI-PLD in the presence of 0.1% Nonidet P-40 substantial GPI anchor degradation (as measured by Triton X-114 phase separation) was observed. The mechanism of this stimulatory effect of detergent was further investigated using [3H]myristate-labelled variant surface glycoprotein and human placental alkaline phosphatase reconstituted into phospholipid vesicles. As with the cell membranes the reconstituted substrates exhibited marked resistance to the action of purified GPI-PLD which could be overcome by the inclusion of Nonidet P-40. Similar results were obtained when crude bovine serum was used as the source of GPI-PLD. These data indicate that the resistance of cell membranes to the action of GPI-PLD is not entirely due to the action of serum or membrane-associated inhibitory factors. A more likely explanation is that, in common with many other eukaryotic phospholipases, the action of GPI-PLD is restricted by the physical state of the phospholipid bilayer in which the substrates are embedded. These data may account for the ability of endothelial and blood cells to retain GPI-anchored proteins on their surfaces in spite of the high levels of GPI-PLD present in plasma.
...
PMID:Factors affecting the ability of glycosylphosphatidylinositol-specific phospholipase D to degrade the membrane anchors of cell surface proteins. 183 78

We have reviewed testes removed from 14 individuals with male pseudohermaphroditism (13 with androgen insensitivity and one with 17 alpha-hydroxylase deficiency) and have studied staining for placental alkaline phosphatase in germ cells. Placental alkaline phosphatase positivity was identified in fetal and premature neonatal controls but not in cryptorchid males or normal autopsy control material from boys older than 6 months. It was present in autopsy testes younger than 6 months and cases of androgen insensitivity in boys younger than 8 months, suggesting immaturity. It was also expressed in two patients with male pseudohermaphroditism aged 5 years and 14 years, both of whom had intra-tubular germ cell neoplasia by morphological criteria. Our study confirms the use of placental alkaline phosphatase as a marker of germ cell neoplasia in this specific group who are at high risk of malignancy.
...
PMID:Germ cell expression of placental alkaline phosphatase in male pseudohermaphroditism. 187 14

Various E. coli strains have been transformed by multicopy plasmids pHI-1, pHI-7 and pPHO I carrying the entire regulatory and structural phoA sequences. All the transformants with the intact pho regulatory system have been shown to be capable of alkaline phosphatase oversynthesis and secretion into the medium. They are also able to accumulate the alkaline phosphatase precursor localized in the outer membrane fraction. The transformants of the restriction or recombination mutants are the most efficient producers of the extracellular enzyme and its precursor.
...
PMID:[Transformation of various strains of Escherichia coli by multicopy plasmids with the phoA gene leads to secretion of a periplasmatic alkaline phosphatase into the media and accumulation of its precursor]. 194 59

A heat-stable alkaline phosphatase, hitherto found in two families with inherited hyperphosphatasemia, was further characterized. The enzyme was similar to serum placental alkaline phosphatase from pregnant women concerning its apparent affinity constant (Km) for 4-nitrophenyl phosphate and its reactivity with H7 monoclonal anti-placental alkaline phosphatase (PLAP) antibodies, but different in the following respects: it exhibited greater heat stability, a higher pH optimum, lower sensitivity to inhibition by L-phenylalanine, and no reactivity with C2 monoclonal anti-PLAP antibodies. The low sensitivity to L-phenylalanine suggests that the enzyme might correspond to a rare phenotype of placental alkaline phosphatase found in human term placenta.
...
PMID:Further characterization of a heat-stable alkaline phosphatase with low sensitivity to L-phenylalanine. 209 73

The immunohistological expression of placental alkaline phosphatase (PLAP) and PLAP-like enzyme was studied in frozen sections from a wide variety (n = 254) of normal and malignant tissues using monoclonal antibodies reactive with PLAP (H317) and PLAP/PLAP-like enzyme (H17E2; H315). PLAP/PLAP-like reactivity was seen in normal thymus, and foetal and neonatal testis, and in 21 out of 22 malignant germ cell tumours (GCTs), but was also found in normal endocervix, normal Fallopian tube and in 28 out of 167 non-GCTs (particularly in ovarian and proximal gastrointestinal tract tumours). Positivity for true PLAP (as demonstrated with H317) was seen in term placenta, in endocervix, and in Fallopian tube (but not in other normal tissues) and was commonly found in ovarian and proximal gastrointestinal tract tumours. Reactivity with H317 was unusual in malignant GCTs (2 out of 22 cases). These findings confirm that PLAP/PLAP-like positivity is a highly sensitive immunohistological marker for malignant GCTs, but one which by itself is of only moderate specificity. Furthermore, expression of true PLAP is rare in GCTs and favours instead an origin from the ovary or proximal gastrointestinal tract. The results also indicate that the predominant heat-stable alkaline phosphatase species in normal foetal and neonatal testis, and in thymus has a similar immunohistological profile to that found in malignant GCTs, and is a PLAP-like enzyme ("germ cell alkaline phosphatase") distinct from true PLAP. The occurrence of this marker in GCTs would appear to reflect increased eutopic production of an enzyme present in trace amount in corresponding normal tissues rather than a genuine example of ectopic expression.
...
PMID:The expression of placental alkaline phosphatase (PLAP) and PLAP-like enzymes in normal and neoplastic human tissues. An immunohistological survey using monoclonal antibodies. 217 80


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---