PMID: 6167984Jun 1, 1981Paper

Asialoglycoprotein receptor mediates the toxic effects of an asialofetuin-diphtheria toxin fragment A conjugate on cultured rat hepatocytes

Proceedings of the National Academy of Sciences of the United States of America
D B CawleyH R Herschman

Abstract

We have constructed a toxic hybrid protein that is recognized by asialoglycoprotein (ASGP) receptors of cultured rat hepatocytes. The conjugate consists of fragment A of diphtheria toxin (DTA) linked by a disulfide bond to asialofetuin (ASF). This conjugate is highly toxic, inhibiting protein synthesis in primary rat hepatocytes at concentrations as low as 10 pM. The ASF-DTA conjugate was 600 and 1800 times as toxic as diphtheria toxin and DTA, respectively, on primary rat hepatocytes. The ASGP receptor recognizes galactose-terminated proteins. We tested a series of glycoproteins for their ability to block the action of the ASF-DTA conjugate. Fetuin and orosomucoid, two glycoproteins with terminal sialic acid on their oligosaccharide chains, did not block the action of the conjugate. Their galactose-terminated asialo derivatives, ASF and asialoorosomucoid, as expected, did block the action of the conjugate. The N-acetylglucosaminyl-terminated derivative (asialogalactoorsomucoid) had no appreciable effect on the activity of the conjugate. We tested the ASF-DTA conjugate on six cell types; except for primary rat hepatocytes, none of them were affected by a high concentration (10 nM) of ASF-DTA conjugate. A fetuin-DTA conjugate wa...Continue Reading

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Citations

Aug 2, 1985·Journal of Immunological Methods·O GrosH Vidal
Jan 1, 1981·Pharmacology & Therapeutics·S Olsnes, A Pihl
Nov 7, 1998·Molecular and Cellular Endocrinology·V BozonR Salesse
May 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·G Y WuR J Stockert
Nov 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·J R MurphyS Nagle
Nov 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J P PerentesisJ R Murphy
Jan 15, 2014·Nucleic Acid Therapeutics·Tatyana N ZamayAnna S Zamay
Aug 31, 2000·Biochemical and Biophysical Research Communications·J S Brooke, J H Cha
Oct 30, 1984·Biochemical and Biophysical Research Communications·H R Herschman
Jun 11, 2011·Circulation Research·Willi Jahnen-DechentMarkus Ketteler
Jan 1, 1982·Immunological Reviews·P E Thorpe, W C Ross
Nov 1, 1985·Scandinavian Journal of Immunology·R Arndt, H J Thiesen
Sep 1, 1985·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·G Y WuM I Rubin
Sep 1, 1985·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·R J Fallon, A L Schwartz
Apr 1, 1989·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·T L Wright
Jan 1, 1984·CRC Critical Reviews in Biochemistry·A L Schwartz
Sep 1, 1983·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·R J Stockert, A G Morell
Nov 11, 2020·Drug Development Research·Selvaraj KunjiappanPanneerselvam Theivendren
Jan 1, 1982·Journal of Cellular Biochemistry·H R HerschmanD B Cawley

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