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. 1989 Mar;86(6):2066–2069. doi: 10.1073/pnas.86.6.2066

Characterization of an amyloid beta precursor protein that binds heparin and contains tyrosine sulfate.

D Schubert 1, M LaCorbiere 1, T Saitoh 1, G Cole 1
PMCID: PMC286848  PMID: 2494659

Abstract

A secreted form of the amyloid beta protein precursor was isolated from the growth conditioned medium of the PC12 sympathetic nerve-like cell line. This protein is recognized by an antiserum that detects a protein of 140 kDa and a less abundant species of 115 kDa on NaDodSO4/acrylamide gels. The amyloid precursor proteins contain O-linked sugars and tyrosine sulfate and bind to the glycosaminoglycan heparin. These results suggest a role for extracellular sulfated glycoproteins in the pathogenesis of Alzheimer disease.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson C. W., Baum P. R., Gesteland R. F. Processing of adenovirus 2-induced proteins. J Virol. 1973 Aug;12(2):241–252. doi: 10.1128/jvi.12.2.241-252.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Candy J. M., Oakley A. E., Klinowski J., Carpenter T. A., Perry R. H., Atack J. R., Perry E. K., Blessed G., Fairbairn A., Edwardson J. A. Aluminosilicates and senile plaque formation in Alzheimer's disease. Lancet. 1986 Feb 15;1(8477):354–357. doi: 10.1016/s0140-6736(86)92319-6. [DOI] [PubMed] [Google Scholar]
  3. Fessler L. I., Brosh S., Chapin S., Fessler J. H. Tyrosine sulfation in precursors of collagen V. J Biol Chem. 1986 Apr 15;261(11):5034–5040. [PubMed] [Google Scholar]
  4. Glenner G. G., Wong C. W. Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun. 1984 Aug 16;122(3):1131–1135. doi: 10.1016/0006-291x(84)91209-9. [DOI] [PubMed] [Google Scholar]
  5. Hortin G., Folz R., Gordon J. I., Strauss A. W. Characterization of sites of tyrosine sulfation in proteins and criteria for predicting their occurrence. Biochem Biophys Res Commun. 1986 Nov 26;141(1):326–333. doi: 10.1016/s0006-291x(86)80372-2. [DOI] [PubMed] [Google Scholar]
  6. Huttner W. B. Determination and occurrence of tyrosine O-sulfate in proteins. Methods Enzymol. 1984;107:200–223. doi: 10.1016/0076-6879(84)07013-0. [DOI] [PubMed] [Google Scholar]
  7. Huttner W. B. Sulphation of tyrosine residues-a widespread modification of proteins. Nature. 1982 Sep 16;299(5880):273–276. doi: 10.1038/299273a0. [DOI] [PubMed] [Google Scholar]
  8. Inestrosa N. C., Matthew W. D., Reiness C. G., Hall Z. W., Reichardt L. F. Atypical distribution of asymmetric acetylcholinesterase in mutant PC12 pheochromocytoma cells lacking a cell surface heparan sulfate proteoglycan. J Neurochem. 1985 Jul;45(1):86–94. doi: 10.1111/j.1471-4159.1985.tb05478.x. [DOI] [PubMed] [Google Scholar]
  9. Kang J., Lemaire H. G., Unterbeck A., Salbaum J. M., Masters C. L., Grzeschik K. H., Multhaup G., Beyreuther K., Müller-Hill B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature. 1987 Feb 19;325(6106):733–736. doi: 10.1038/325733a0. [DOI] [PubMed] [Google Scholar]
  10. Masters C. L., Simms G., Weinman N. A., Multhaup G., McDonald B. L., Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4245–4249. doi: 10.1073/pnas.82.12.4245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rosa P., Hille A., Lee R. W., Zanini A., De Camilli P., Huttner W. B. Secretogranins I and II: two tyrosine-sulfated secretory proteins common to a variety of cells secreting peptides by the regulated pathway. J Cell Biol. 1985 Nov;101(5 Pt 1):1999–2011. doi: 10.1083/jcb.101.5.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ross A. H., Cossu G., Herlyn M., Bell J. R., Steplewski Z., Koprowski H. Isolation and chemical characterization of a melanoma-associated proteoglycan antigen. Arch Biochem Biophys. 1983 Aug;225(1):370–383. doi: 10.1016/0003-9861(83)90042-5. [DOI] [PubMed] [Google Scholar]
  13. Schubert D., LaCorbiere M. Isolation of a cell-surface receptor for chick neural retina adherons. J Cell Biol. 1985 Jan;100(1):56–63. doi: 10.1083/jcb.100.1.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schubert D., Schroeder R., LaCorbiere M., Saitoh T., Cole G. Amyloid beta protein precursor is possibly a heparan sulfate proteoglycan core protein. Science. 1988 Jul 8;241(4862):223–226. doi: 10.1126/science.2968652. [DOI] [PubMed] [Google Scholar]
  15. Selkoe D. J., Podlisny M. B., Joachim C. L., Vickers E. A., Lee G., Fritz L. C., Oltersdorf T. Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7341–7345. doi: 10.1073/pnas.85.19.7341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Shivers B. D., Hilbich C., Multhaup G., Salbaum M., Beyreuther K., Seeburg P. H. Alzheimer's disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact. EMBO J. 1988 May;7(5):1365–1370. doi: 10.1002/j.1460-2075.1988.tb02952.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Snow A. D., Willmer J. P., Kisilevsky R. Sulfated glycosaminoglycans in Alzheimer's disease. Hum Pathol. 1987 May;18(5):506–510. doi: 10.1016/s0046-8177(87)80036-9. [DOI] [PubMed] [Google Scholar]
  18. Snow A. D., Willmer J., Kisilevsky R. Sulfated glycosaminoglycans: a common constituent of all amyloids? Lab Invest. 1987 Jan;56(1):120–123. [PubMed] [Google Scholar]

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