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Gene Review

ALPI  -  alkaline phosphatase, intestinal

Homo sapiens

Synonyms: IAP, Intestinal alkaline phosphatase, Intestinal-type alkaline phosphatase

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Disease relevance of ALPI


Psychiatry related information on ALPI


High impact information on ALPI

  • Moreover, overexpression of PTEN, which antagonizes PI3K, significantly augmented the induction of IAP enzyme activity in HT29 and Caco-2 cells treated with sodium butyrate and in spontaneously differentiated Caco-2 cells [7].
  • Brush-border enzyme (intestinal alkaline phosphatase [IAP] and sucrase) activities, IAP messenger RNA levels, and IAP promoter induction were measured [7].
  • Indeed, the membrane-anchored IAP Ig variable domain suffices to mediate Vn particle binding in this system, while the multiply membrane-spanning and cytoplasmic domains are dispensable [8].
  • To better determine the function of IAP, we have characterized and used an IAP-deficient human cell line [8].
  • These data demonstrate that some alpha v integrin ligand-binding functions are IAP independent, whereas others require IAP, presumably through direct physical interaction between its Ig domain and the integrin [8].

Chemical compound and disease context of ALPI

  • When the islets of NON mice were incubated with or without IL-1 (10 U/ml) in the presence of high glucose, IAP was rarely found in beta-cells and retrovirus type C was undetectable in beta-cells [5].

Biological context of ALPI

  • Furthermore, from a comparison of our data with the linkage map of the syntenic region on mouse chromosome 1, we conclude that the t(2;13) breakpoint is most closely flanked by loci INHA and ALPI within this map interval [9].
  • Transient transfections with IAP-luciferase reporter constructs were used to characterize the mechanisms by which KLF4 activates IAP transcription [10].
  • IAP transactivation by KLF4 is likely mediated through a critical region located within the proximal IAP promoter region [10].
  • Transfections with a variety of IAP-luciferase reporter constructs were used to identify a Cdx response element located within the human IAP gene promoter [1].
  • This sensitization to TNF-alpha-induced killing was attributable to suppression of IAP (inhibitors of apoptosis) production known to be regulated by the cytoprotective nuclear factor-kappaB-dependent arm of TNF-alpha signaling [11].

Anatomical context of ALPI

  • To identify new putative promoter motifs responsible for the regulation of ALPI expression during differentiation of the enterocytes, we have conducted a computer-assisted cis-element search of the proximal human ALPI promoter sequence [12].
  • The intestinal alkaline phosphatase gene (ALPI) encodes a digestive brush-border enzyme, which is highly upregulated during small intestinal epithelial cell differentiation [12].
  • The ability of HNF-4alpha to stimulate the expression from the ALPI promoter was investigated in the nonintestinal Hela cell line [12].
  • Transient transfection studies with luciferase reporter plasmids carrying various internal and 5' deletion mutations of the IAP promoter localized a putative thyroid hormone response element (TRE) to a region approximately 620 nucleotides upstream (-620) of the ATG start codon [13].
  • The highest IAP levels were found in 2 yolk-sac tumors [14].

Associations of ALPI with chemical compounds

  • This dramatic loss of IAP expression from tumor stroma/vasculature may form a strong basis for explaining amifostine selectivity [15].
  • In contrast, the abundance of IAP expression in normal tissues, stromal and vascular, ensures an intense hydrolysis of WR-2721 and rapid intracellular accumulation of WR-1065 [15].
  • The thyroid hormone receptor complex and KLF4 synergistically activate the enterocyte differentiation marker gene IAP, suggesting a previously unrecognized interrelationship between these two transcription factor pathways [16].
  • Concomitant treatment with T3 and butyric acid produced an additive effect on IAP transactivation [17].
  • To evaluate a possible quantitative relationship between the rise in intestinal alkaline phosphatase (IAP) activity and triglyceride-rich lipoproteins in the blood after an oral fat intake, a specific and sensitive immunocatalytic assay was used [18].

Other interactions of ALPI

  • There are at least three alkaline phosphatase (AP) isoenzymes in man: a heat-stable placental enzyme (PLAP), a less heat-stable intestinal form (IAP), and the very heat-labile AP enriched in liver, bone and kidney [19].
  • We used fluorescence in situ hybridization (FISH) to map ALPI (intestinal alkaline phosphatase) to 2q36.3-q37.1 and FN1 to 2q34 [20].
  • Functional analysis revealed that Cdx1 transactivates (fourfold, P < 0.05) the IAP promoter through a novel Cdx response element (GTTTAGA) located between -2369 and -2375 upstream of the translational start site [1].
  • To define the structural differences between these isozymes, we have built models of the TNAP, IAP, and GCAP molecules based on the 1.8-structure of PLAP(1) and have performed a comparative structural analysis [21].
  • Median enzyme concentration were increased in 'poor' compared to 'good' prognosis patients: start IAP 3.2 versus 2.2 U/g creat (NS), start NAG 48.6 versus 13.7 (P < 0.01), start TNAP 3.5 versus 0.9 (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)[3]

Analytical, diagnostic and therapeutic context of ALPI


  1. Differential regulation of intestinal alkaline phosphatase gene expression by Cdx1 and Cdx2. Alkhoury, F., Malo, M.S., Mozumder, M., Mostafa, G., Hodin, R.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  2. The ALPI Trial: the Italian/European experience with adjuvant chemotherapy in resectable non-small lung cancer. Scagliotti, G.V. Clin. Cancer Res. (2005) [Pubmed]
  3. Urinary enzymes in acute renal failure. Chew, S.L., Lins, R.L., Daelemans, R., Nuyts, G.D., De Broe, M.E. Nephrol. Dial. Transplant. (1993) [Pubmed]
  4. Identification of differentially expressed genes following treatment of monkey kidney cells with the mycotoxin fumonisin B(1). Zhang, Y., Jones, C., Dickman, M.B. Food Chem. Toxicol. (2001) [Pubmed]
  5. IL-1 induces intracisternal type A virus and retrovirus type C in pancreatic beta-cells of NOD mice. Tsumara, H., Wang, J.Z., Ogawa, S., Ohota, H., Komada, H., Ito, Y., Shimura, K. J. Exp. Anim. Sci. (1994) [Pubmed]
  6. Gamma-glutamyl transferase, intestinal alkaline phosphatase and beta-hexosaminidase activity in duodenal biopsies from chronic alcoholics. Hauge, T., Nilsson, A., Persson, J., Hultberg, B. Hepatogastroenterology (1998) [Pubmed]
  7. Inhibition of the phosphatidylinositol 3-kinase pathway contributes to HT29 and Caco-2 intestinal cell differentiation. Wang, Q., Wang, X., Hernandez, A., Kim, S., Evers, B.M. Gastroenterology (2001) [Pubmed]
  8. Integrin-associated protein immunoglobulin domain is necessary for efficient vitronectin bead binding. Lindberg, F.P., Gresham, H.D., Reinhold, M.I., Brown, E.J. J. Cell Biol. (1996) [Pubmed]
  9. Localization of the t(2;13) breakpoint of alveolar rhabdomyosarcoma on a physical map of chromosome 2. Barr, F.G., Holick, J., Nycum, L., Biegel, J.A., Emanuel, B.S. Genomics (1992) [Pubmed]
  10. Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor. Hinnebusch, B.F., Siddique, A., Henderson, J.W., Malo, M.S., Zhang, W., Athaide, C.P., Abedrapo, M.A., Chen, X., Yang, V.W., Hodin, R.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  11. Response of hairy cells to IFN-alpha involves induction of apoptosis through autocrine TNF-alpha and protection by adhesion. Baker, P.K., Pettitt, A.R., Slupsky, J.R., Chen, H.J., Glenn, M.A., Zuzel, M., Cawley, J.C. Blood (2002) [Pubmed]
  12. Differentiation-dependent activation of the human intestinal alkaline phosphatase promoter by HNF-4 in intestinal cells. Olsen, L., Bressendorff, S., Troelsen, J.T., Olsen, J. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  13. Thyroid hormone positively regulates the enterocyte differentiation marker intestinal alkaline phosphatase gene via an atypical response element. Malo, M.S., Zhang, W., Alkhoury, F., Pushpakaran, P., Abedrapo, M.A., Mozumder, M., Fleming, E., Siddique, A., Henderson, J.W., Hodin, R.A. Mol. Endocrinol. (2004) [Pubmed]
  14. Patterns of seminoma tissue markers and deletions. Yamamoto, H., Rudén, U., Ljungdahl-Ståhle, E., Brehmer-Andersson, E., Hirano, K., Hisazumi, H., Stigbrand, T., Wahren, B. Int. J. Cancer (1987) [Pubmed]
  15. Down-regulation of intestinal-type alkaline phosphatase in the tumor vasculature and stroma provides a strong basis for explaining amifostine selectivity. Giatromanolaki, A., Sivridis, E., Maltezos, E., Koukourakis, M.I. Semin. Oncol. (2002) [Pubmed]
  16. Convergence of the thyroid hormone and gut-enriched Krüppel-like factor pathways in the context of enterocyte differentiation. Siddique, A., Malo, M.S., Ocuin, L.M., Hinnebusch, B.F., Abedrapo, M.A., Henderson, J.W., Zhang, W., Mozumder, M., Yang, V.W., Hodin, R.A. J. Gastrointest. Surg. (2003) [Pubmed]
  17. Short-chain fatty acids and thyroid hormone interact in regulating enterocyte gene transcription. Meng, S., Wu, J.T., Archer, S.Y., Hodin, R.A. Surgery (1999) [Pubmed]
  18. Human intestinal alkaline phosphatase--release to the blood is linked to lipid absorption, but removal from the blood is not linked to lipoprotein clearance. Domar, U., Karpe, F., Hamsten, A., Stigbrand, T., Olivecrona, T. Eur. J. Clin. Invest. (1993) [Pubmed]
  19. Two gene duplication events in the evolution of the human heat-stable alkaline phosphatases. Knoll, B.J., Rothblum, K.N., Longley, M. Gene (1987) [Pubmed]
  20. In situ hybridization applied to Waardenburg syndrome. Wu, B.L., Milunsky, A., Wyandt, H., Hoth, C., Baldwin, C., Skare, J. Cytogenet. Cell Genet. (1993) [Pubmed]
  21. Structural evidence of functional divergence in human alkaline phosphatases. Le Du, M.H., Millan, J.L. J. Biol. Chem. (2002) [Pubmed]
  22. Rat enterocytes secrete SLPs containing alkaline phosphatase and cubilin in response to corn oil feeding. Mahmood, A., Shao, J.S., Alpers, D.H. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  23. Intestinal alkaline phosphatase gene expression is activated by ZBP-89. Malo, M.S., Mozumder, M., Zhang, X.B., Biswas, S., Chen, A., Bai, L.C., Merchant, J.L., Hodin, R.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
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