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)

The cytoplasmic beta-catenin protein is implicated in signal transduction and associates with both the cell-cell adhesion protein E-cadherin and the tumor suppressor gene product APC. We determined the primary structure of the human beta-catenin gene (CTNNB1) by analysis of cDNA and genomic clones. The size of the complete gene was determined to be 23.2 kb. Restriction mapping and partial sequence analysis revealed 16 exons. All splice donor and acceptor sites were conformable to the GT/AG rule. The exon size ranged from 61 to 790 bp. Half of the introns were smaller than 550 bp, with the smallest being 84 bp and the longest being 6700 bp. The intron-exon boundaries did not coincide either with conserved sites in the 12 armadillo repeat sequences of beta-catenin or with intron-exon boundaries in the armadillo gene of Drosophila. A major site for transcription initiation was identified as an A residue 214 nucleotides upstream of the ATG initiation codon. The resulting transcript is 3362 nucleotides long. Compared to the previously published mRNA sequence, additional residues were identified, 16 at the 5' end and 766 at the 3' end of the mRNA. An alternative splice acceptor site within exon 16 reduced the 3' UTR sequence by 159 bp. Polymerase chain reaction on cDNA from 14 human cell lines demonstrated the general occurrence of both splice variants. The 5'-flanking region is highly GC-rich and lacks a CCAAT box, but contains a TATA box and potential binding sites for several transcription factors, such as NF kappa B, SP1, AP2, and EGR1. Both a 437-bp fragment and a 6-kb fragment, containing about 4.7 kb of the 5'-flanking region in addition to the noncoding exon 1 and 1 kb of intron 1, showed clear promoter activity when these fragments were linked to a secreted alkaline phosphatase reporter gene and transfected into a mouse epithelial cell line.
...
PMID:Genomic organization of the human beta-catenin gene (CTNNB1). 883 5

Direct cell-cell interactions are fundamental for tissue development and differentiation. We have studied the expression and function of cadherins in human osteoblasts during in vitro differentiation. Using reverse transcription-polymerase chain reaction and mRNA hybridization, we found that human trabecular bone osteoblasts (HOBs), osteoprogenitor marrow stromal cells (BMCs), and the osteogenic sarcoma lines, SaOS-2 and MG-63, expressed mRNA for cadherin-11 (C11) and N-cadherin (N-cad). HOBs and BMCs also expressed low levels of cadherin-4 (C4) mRNA. C11 was the most abundant cadherin protein present in human osteoblasts, and its expression was unaffected by bone morphogenetic protein-2 (BMP-2) treatment of either BMCs or HOBs. Likewise, N-cad mRNA did not change during BMP-2 incubation. Conversely, C4 protein, undetectable in transformed cell lines, was down-regulated by BMP-2 treatment of normal cells. Both C11 and C4 were localized to sites of cell-cell contact in both HOBs and BMCs, colocalized with beta-catenin, and bands corresponding to cadherins were coimmunoprecipitated by a beta-catenin antibody, findings indicative of functional cadherins. A decapeptide containing the HAV motif of human N-cad partially inhibited Ca2+-dependent cell-cell adhesion and completely prevented BMP-2-induced stimulation of alkaline phosphatase activity by BMCs. Thus, human osteoblasts and their progenitor cells express a repertoire of multiple cadherins. Cadherin-mediated cell-to-cell adhesion is critical for normal human osteoblast differentiation.
...
PMID:Human osteoblasts express a repertoire of cadherins, which are critical for BMP-2-induced osteogenic differentiation. 955 63

Mutation of the adenomatous polyposis coli (APC) gene is associated with the earliest stages of colorectal tumorigenesis and appears to be responsible for the hereditary condition familial adenomatous polyposis (FAP). Evidence indicates that cyclooxygenase-2 (COX-2) is induced and at elevated levels in human colorectal cancers and in the polyps of mouse FAP models. We have used HT-29 cells, a human colorectal carcinoma cell line with a mutant carboxy-truncated APC gene, in which intact APC gene has been introduced under the control of an inducible promoter. These HT-29-APC cells provide a suitable model system to examine how COX-2 expression becomes dysregulated after loss of APC function. Induction of full-length APC causes the HT-29-APC cells to undergo apoptosis. However, differentiation, as measured by alkaline phosphatase activity, is not induced upon expression of full-length APC. Full-length APC protein has been shown to bind the intracellular protein beta-catenin and, as a result, the Lef/Tcf transcription factors are down-regulated. Analysis of APC immunoprecipitates demonstrate a time-dependent increase of beta-catenin interacting with full-length APC. Thus, the Lef/Tcf signaling pathway is intact at this point in these cells. Furthermore, upon expression of full-length APC, COX-2 protein expression is down-regulated while COX-2 mRNA levels remain the same. These data indicate that APC plays a role, either directly or indirectly, in the translational regulation of COX-2. Treatment of the HT-29-APC cells with sodium butyrate, an inducer of apoptosis, does not alter COX-2 protein expression. Thus, COX-2 down-regulation appears to be APC specific and not just due to apoptotic induction. APC appears to uniquely regulate COX-2 expression. The mechanism by which COX-2 protein expression is down-regulated in the HT-29-APC cells is under investigation.
...
PMID:Introduction of full-length APC modulates cyclooxygenase-2 expression in HT-29 human colorectal carcinoma cells at the translational level. 1054 4

Cell-to-cell adhesion, an important event in differentiation, is impaired during advanced stages of tumorigenesis. In this study, we examined the possible regulation of cell-adhesion proteins by the differentiation agent butyrate in LS174T and HM7 cells, two types of human colon cancer cells that differ in their ability to produce mucin and colonize the liver of experimental animals. The more aggressive, high-mucin-producing cell line (HM7), a clone selected from LS174T cells, showed a scattered and undifferentiated ultramorphological appearance and low basal alkaline phosphatase activity; the proteins beta-catenin and E-cadherin, as detected by immunostaining, were expressed in the cells' nuclei. All of these properties were significantly less pronounced in the less aggressive, low-mucin-producing LS174T cells. In both cell lines, butyrate treatment enhanced cell-to-cell interaction, alkaline phosphate activity, translocation of beta-catenin and E-cadherin from the nuclei to the membrane junctions, and transcription and translation of the 120-kDa E-cadherin isoform, but not of its 100-kDa isoform. Analysis of possible mechanisms of E-cadherin up-regulation revealed that butyrate induces the release of nuclear proteins from the E-cadherin promoter sequence, reducing transcription repression. We suggest that butyrate activates E-cadherin transcription through translocation of nuclear transcription factors bearing specific repressor activity. We surmise that abrogation of nuclear 100-kDa E-cadherin and beta-catenin expression following butyrate treatment is related to the control of E-cadherin gene transcription.
...
PMID:Butyrate regulates E-cadherin transcription, isoform expression and intracellular position in colon cancer cells. 1063 89

Accumulation of intracellular beta-catenin, as a result of inactivation of the adenomatous polyposis coli (APC) gene or by mutation of the beta-catenin gene (CTNNB1) itself, is involved in a wide range of human cancers. By means of fluorescent differential display using a murine fibroblast cell line (L-MT), which expresses an activated form of beta-catenin that accumulates in the cells, we found that expression of murine monocyte chemotactic protein-3 (mMCP-3) was suppressed by activated beta-catenin. Inversely, expression of MCP-3 in human colon cancer cells was induced by depletion of beta-catenin after adenovirus-mediated transfer of wild-type APC genes into the cells. A reporter-gene assay indicated that the accumulation of beta-catenin in the nucleus suppressed activity of the MCP-3 promoter through a putative T-cell factor/lymphocyte enhancer factor (Tcf/LEF)-binding site, ATCAAAG; but when the promoter sequence contained a two-base substitution in the binding site, it failed to suppress reporter-gene (luciferase) activity. An electrophoretic mobility-shift assay using the putative Tcf/LEF-binding sequence revealed interaction of the candidate sequence with the beta-catenin complex. Furthermore, induction of MCP-3 cDNA into HT-29 colon cancer cells increased expression of two markers of differentiation: alkaline phosphatase and carcinoembryonic antigen. Our results implied that activation of beta-catenin through the Tcf/LEF signaling pathway may participate in colonic carcinogenesis by inhibiting MCP-3-induced differentiation of colorectal epithelial cells.
...
PMID:Down-regulation of monocyte chemotactic protein-3 by activated beta-catenin. 1111 53

The beta-catenin TCF pathway is implicated in the regulation of colonic epithelial cell proliferation, but its role in the regulation of cell differentiation is unknown. The colon carcinoma cell line, Caco-2, spontaneously undergoes G(0)/G(1) cell cycle arrest and differentiates along the absorptive cell lineage over 21 days in culture. In parallel, we show that beta-catenin-TCF activity and complex formation are significantly down-regulated. The down-regulation of beta-catenin-TCF signaling was independent of APC, which we characterized as having a nonsense mutation in codon 1367 in Caco-2 cells, but was associated with a decrease in TCF-4 protein levels. Total beta-catenin levels increased during Caco-2 cell differentiation, although this was attributable to an increase in the membrane, E-cadherin-associated, fraction of beta-catenin. Importantly, down-regulation of beta-catenin-TCF signaling in undifferentiated Caco-2 cells by three different mechanisms, ectopic expression of E-cadherin, wild-type APC, or dominant negative TCF-4, resulted in an increase in the promoter activities of two genes that are well-established markers of cell differentiation, alkaline phosphatase and intestinal fatty acid binding protein. These studies demonstrate, therefore, that in addition to its established role in the regulation of cell proliferation, down-regulation of the beta-catenin-TCF pathway is associated with the promotion of a more-differentiated phenotype in colonic epithelial cells.
...
PMID:Down-regulation of beta-catenin TCF signaling is linked to colonic epithelial cell differentiation. 1130 9

First, using morpholino against lacZ, we demonstrate that the morpholino specifically suppresses the translation of the gene introduced exogenously into Ciona eggs. Second, using morpholino against an alkaline phosphatase gene, we show that the morpholino suppresses the translation of the endogenous gene as well. Third, using morpholino against beta-catenin gene, we confirm that the suppression by the morpholino can be rescued by injection of beta-catenin mRNA. All of these results indicate that morpholino act in Ciona embryos to specifically block the function of endogenous genes as well as exogenously introduced genes. genesis 30: 103--106, 2001.
...
PMID:Action of morpholinos in Ciona embryos. 1147 83

In early Ciona embryos, nuclear accumulation of beta-catenin is most probably the first step of endodermal cell specification. If beta-catenin is mis- and/or overexpressed, presumptive notochord cells and epidermal cells change their fates into endodermal cells, whereas if beta-catenin nuclear localization is downregulated by the overexpression of cadherin, the endoderm differentiation is suppressed, accompanied with the differentiation of extra epidermal cells ( Imai, K., Takada, N., Satoh, N. and Satou, Y. (2000) Development 127, 3009-3020). Subtractive hybridization screens of mRNAs between beta-catenin overexpressed embryos and cadherin overexpressed embryos were conducted to identify potential beta-catenin target genes that are responsible for endoderm differentiation in Ciona savignyi embryos. We found that a LIM-homeobox gene (Cs-lhx3), an otx homolog (Cs-otx) and an NK-2 class gene (Cs-ttf1) were among beta-catenin downstream genes. In situ hybridization signals for early zygotic expression of Cs-lhx3 were evident only in the presumptive endodermal cells as early as the 32-cell stage, those of Cs-otx in the mesoendodermal cells at the 32-cell stage and those of Cs-ttf1 in the endodermal cells at the 64-cell stage. Later, Cs-lhx3 was expressed again in a set of neuronal cells in the tailbud embryo, while Cs-otx was expressed in the anterior nervous system of the embryo. Expression of all three genes was upregulated in beta-catenin overexpressed embryos and downregulated in cadherin overexpressed embryos. Injection of morpholino oligonucleotides against Cs-otx did not affect the embryonic endoderm differentiation, although the formation of the central nervous system was suppressed. Injection of Cs-ttf1 morpholino oligonucleotides also failed to suppress the endoderm differentiation, although injection of its synthetic mRNAs resulted in ectopic development of endoderm differentiation marker alkaline phosphatase. By contrast, injection of Cs-lhx3 morpholino oligo suppressed the endodermal cell differentiation and this suppression was rescued by injection of Cs-lhx3 mRNA into eggs. In addition, although injection of delE-Ci-cadherin mRNA into eggs resulted in the suppression of alkaline phosphatase development, injection of delE-Ci-cadherin mRNA with Cs-lhx3 mRNA rescued the alkaline phosphatase development. These results strongly suggest that a LIM-homeobox gene Cs-lhx3 is one of the beta-catenin downstream genes and that its early expression in embryonic endodermal cells is responsible for their differentiation.
...
PMID:Early embryonic expression of a LIM-homeobox gene Cs-lhx3 is downstream of beta-catenin and responsible for the endoderm differentiation in Ciona savignyi embryos. 1156 60

Increasing evidence suggests that morphogenesis of the distinct developmental structures derived from the same organ-committed epithelium is controlled by differential mechanisms. As was recently shown in mice with mutations in the downless (dL) gene, induction of primary or tylotrich hair follicles is strikingly dependent of signaling through the Tnf receptor homologue, Edar. Here, we show that dorsal skin of murine embryos with constitutive deletion of the BMP2/4 antagonist noggin, after transplantation into SCID mice, is characterized by the lack of induction of secondary hair follicles, and by the arrest of primary hair follicle development prior to hair shaft formation. The loss of noggin activity was associated with failure to express genes that specify hair follicle cell fates in the epidermis (Lef-1, beta-catenin, Shh) and dermal papilla (p75 kDa neurotrophin receptor, alkaline phosphatase). This suggests that regulation of BMP2/4 signaling by noggin is essential for the induction of secondary hair follicles, as well as for advanced stages of development in primary hair follicles.
...
PMID:Modulation of BMP signaling by noggin is required for induction of the secondary (nontylotrich) hair follicles. 1185 69

Wnt glycoproteins are important regulators of cellular differentiation and embryonic development. Some Wnt proteins induce stabilization of beta-catenin which cooperatively regulates gene expression with LEF/Tcf transcription factors. Here we demonstrate a direct role for beta-catenin signaling in osteoblast differentiation and in BMP2-mediated signal transduction. Similar to treatment with BMP-2 protein, ectopic expression of stabilized beta-catenin in C3H10T1/2 cells or activation of endogenous beta-catenin signaling with LiCl induces expression of alkaline phosphatase mRNA and protein, a defined marker of early osteoblast differentiation. Unlike BMP2 protein, stabilized beta-catenin does not induce osteocalcin gene expression, a marker of late osteoblast differentiation. BMP2-induced differentiation also leads to activation of endogenous beta-catenin signaling thus implicating beta-catenin in early steps of BMP2-mediated osteoblast differentiation. Effects of beta-catenin and BMP2 on C3H10T1/2 differentiation are not completely overlapping, implying that some aspects of BMP2-induced differentiation may be mediated by beta-catenin signaling and that beta-catenin can also participate in non-BMP2-dependent differentiation processes.
...
PMID:Activated beta-catenin induces osteoblast differentiation of C3H10T1/2 cells and participates in BMP2 mediated signal transduction. 1253 44


1 2 3 4 5 6 7 8 Next >>

---