Disease relevance of Akp1

• Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia [1].
• Alkaline phosphatase (E.C.3.1.3.1.) has been used as a marker for embryonal carcinoma cells which constitute the multipotential stem cells of the mouse teratoma [2].
• Studies by other investigators based on kinetics of thermal inactivation and L-phenylalanine inhibition have shown that the alkaline phosphatase of the teratoma differs from the mouse intestinal and liver isozymes, but resembles the isozymes of kidney and placenta [2].
• Monitoring of murine osteosarcoma by serial alkaline phosphatase determinations [3].
• Association of alkaline phosphatase with an autoantigen recognised by circulating anti-neutrophil antibodies in systemic vasculitis [4].

Psychiatry related information on Akp1

• ALP converted disodium phenyl phosphate into its product, phenol, at a relatively high reaction rate without consumption, with resultant amplification of the signal on prolonged reaction time, producing an adequate amount of product for final detection [5].
• During gestation ALP-specific activity peaked at Day 7 to 8 (Day 1 is day of detection of the copulation plug) followed by a rapid decline to control levels by Day 9 [6].

High impact information on Akp1

• An Flp indicator mouse expressing alkaline phosphatase from the ROSA26 locus [7].
• Osteoblasts from both stromal and calvarial explants showed delayed maturation in vitro as measured by expression of alkaline phosphatase (ALP), induction of mRNA encoding osteocalcin and mineral deposition [8].
• Binding activity detected with alkaline phosphatase fusions of ELF-1 and Mek4 also reveals gradients and provides direct evidence for molecular complementarity of gradients in reciprocal fields [9].
• They form colonies of densely packed, alkaline phosphatase-positive, SSEA-1-positive cells resembling undifferentiated embryonic stem (ES) cells in morphology [10].
• The differentiation of the osteoblastic phenotype was stimulated as determined by increased alkaline phosphatase production and the deposition of mineral [11].

Chemical compound and disease context of Akp1

• In addition, a high level of serum alkaline phosphatase, low 1,25-dihydroxyvitamin D, deformity of bone, and impairment of body weight gain became evident [12].
• Alkaline phosphatase [orthophosphoricmonoester phosphohydrolase (alkaline pH optimum), EC 3.1.3.1] purified from a Burkitt lymphoma cell line (Daudi) and Moloney-virus-induced murine leukemia (YAC) showed unique catalytic properties in substrate specificity and inhibition by cysteamine-S-phosphate [13].
• Three spontaneous salivary myoepitheliomas in BALB/c mice were also analyzed; two different lactate dehydrogenase profiles were observed, and all three tumors lacked the placental alkaline phosphatase present in polyoma virus-induced salivary tumors [14].
• An organ-specific alkaline phosphatase inhibitor, L-homoarginine, at 44.5 mM concentration inhibited [3H]thymidine uptake by C3H/He mouse osteosarcoma (OS) cells, while L-arginine, L-phenylalanine, and glycine had little effect on the uptake [15].
• Alkaline phosphatase activities of 6-thiopurine-sensitive and -resistant sublines of Sarcoma 180 [16].

Biological context of Akp1

• The gene encoding C9.1 antigen was linked to the Akp1 isozyme locus on chromosome 1 close to the 2B4 gene [17].
• This study suggests that the reduced ALP activity after skeletal unloading is related to downregulation of PECAM-1 expression in bone marrow cells in mice [18].
• All three mouse genes are composed of 11 exons interrupted by 10 small introns (70-261 bp) with an organization analogous to that of the three human tissue-specific AP genes [19].
• Introns interrupt the coding sequences at identical positions in all three mouse and human tissue-specific AP genes [19].
• A repetitive sequence inserted in exon XI of the mouse intestinal AP gene codes for a unique stretch of 41 amino acids, 20 of which are threonines [19].

Anatomical context of Akp1

• CONCLUSIONS: Our data show that the reduced ALP activity after skeletal unloading is closely correlated with reduced expression of PECAM-1 in bone marrow cells [18].
• This insertion has disrupted a region recognized as being responsible for phosphatidylinositol anchorage of human placental AP to the cytoplasmic membrane [19].
• Electron microscopy and histochemical analysis of odontoblast markers showed that differentiated cells induced by FGF1+TGFbeta1 exhibited cytological features of functional odontoblasts with matrix vesicle secretion and mineral formation, positive alkaline-phosphatase activity, and type-I collagen production [20].
• The cartilaginous cells and surrounding cells in the processes are all alkaline phosphatase-positive and surrounded by the common periosteum, suggesting that progenitor cells of the processes, dentary ramus and secondary cartilages all originate from a common pool [21].
• Nonhypertrophied chondrocytes of Meckel's cartilage express alkaline phosphatase at stage M23 [21].

Associations of Akp1 with chemical compounds

• Genetic variation in alkaline phosphatase of the house mouse (Mus musculus) with emphasis on a manganese-requiring isozyme [22].
• The areal and laminar distribution of AP activity matches that of the GAD(65), the GABA synthesizing enzyme found in presynatic terminals [23].
• These colonies had alkaline phosphatase activity and incorporated 5-bromo-2'-deoxyuridine [24].
• Intimately linked to this process is alkaline phosphatase (AP), a cell-surface glycoprotein that possibly functions as a transport protein [25].
• Differences between strains of mice were observed in electrophoretic migration on cellulose acetate plates of alkaline phosphatase in butanol extracts of kidney, bone and placenta [26].

Physical interactions of Akp1

• The same alkaline phosphatase treatment completely abolished the DNA-binding properties of the c-fos cyclic AMP-responsive element-specific proteins [27].
• In the osteoblastic cell line, MC3T3-E1, continuous treatment with cAMP elevating agents inhibited both osteoblastic differentiation based on alkaline phosphatase assay and DNA binding ability of Cbfa1 based on a gel retardation assay [28].
• The wild type neurocan hyaluronan binding domain fused to alkaline phosphatase bound to immobilized hyaluronan under physiological as well as moderately hypertonic conditions, whereas its ability to bind to immobilized chondroitin sulfate dropped rapidly with increasing salt concentration [29].
• Hepa-1 nuclear Ah receptor could not be converted to a smaller ligand-binding subunit by treatment with alkaline phosphatase, ribonuclease, or sulfhydryl-modifying reagents or prolonged exposure to 1.0 M KCl [30].
• This inference was confirmed by direct binding assays in which particulate titanium coated with adsorbed collagenase bound an alkaline phosphatase conjugated anti-collagenase antibody, but not a conjugated anti-IgG antibody [31].

Regulatory relationships of Akp1

• Anti-PECAM-1 antibody inhibited the increase in ALP production under co-culture with EOMA [18].
• Serum alkaline phosphatase activity is regulated by a chromosomal region containing the alkaline phosphatase 2 gene (Akp2) in C57BL/6J and DBA/2J mice [32].
• Igf1 null hypertrophic chondrocytes differentiate normally in terms of expressing specialized proteins such as collagen X and alkaline phosphatase, but are smaller than wild-type at all levels of the hypertrophic zone [33].
• Introduction of Msx2 induced alkaline phosphatase activity in C3H10T1/2 and C2C12 cells and promoted the calcification of murine primary osteoblasts [34].
• Similarly, ectopic expression of MyoD in the pluripotent mesenchymal cell line C3H10T1/2 increased alkaline phosphatase activity induced by BMP-7 [35].

Other interactions of Akp1

• A variety of sequence polymorphisms in this chromosomal region could be responsible for the differences in serum AP activity; the Akp2 gene, however, with several known amino acid substitutions between protein sequences of the B6 and D2 strains, is a leading candidate [32].
• Sas-2 was located by linkage analysis between Idh-1 locus and Akp-1 locus on chromosome 1 [36].
• A manganese-requiring isozyme of liver and kidney unaffected by neuraminidase is described, and the locus controlling variation in this isozyme is designated Akp-1 [22].
• Incubating primary muscle cells with 300 ng/ml of BMP-2 for 6 d also inhibited myotube formation, whereas induced ALP activity and osteocalcin production [37].
• We report the inactivation, via homologous recombination, of two of the three active mouse alkaline phosphatase genes, i.e., embryonic (EAP) and tissue nonspecific (TNAP) [38].

Analytical, diagnostic and therapeutic context of Akp1

• A new electrophoretic migration type of alkaline phosphatase 1 (Akp1) was found on the cellulose acetate electrophoresis for kidney and liver homogenates of KWHM mouse, a newly established inbred strain derived from the Korean wild mouse (Mus musculus molossinus) [39].
• Analysis of the purified cells by alkaline phosphatase staining and immunocytochemistry with anti-c-kit antibody demonstrated that highly (98%) purified PGCs can be isolated using this method [40].
• Studies, using RT-PCR analysis, of the expression pattern of the alkaline phosphatase isoenzymes which serve as markers for testicular germ cell tumors demonstrated that the expression of the endogenous mouse embryonic alkaline phosphatase (EAP) is upregulated in the GC-1spg cell line [41].
• By employing a quantitative immunoassay system, it was found that the Ly-31.1-specific antibody detected an allotypic determinant of mouse alkaline phosphatase [42].
• Expression of alkaline phosphatase in the mature mouse placenta visualized by in situ hybridization and enzyme histochemistry [43].

References