Fatty acylation of heparan sulfate proteoglycan from human colon carcinoma cells

Renato V. Iozzo, I. Kovalszky, Nina Hacobian, Paul K. Schick, John S. Ellingson, George R. Dodge

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

A number of transmembrane proteins have been recently reported to be modified by the covalent addition of saturated fatty acids which may contribute to membrane targeting and specific protein-lipid interactions. Such modifications have not been reported in cell-associated heparan sulfate proteoglycans, although these macromolecules are known to be hydrophobic. Here, we report that a cell surface heparan sulfate proteoglycan is acylated with both myristate and palmitate, two long-chain saturated fatty acids. When colon carcinoma cells were labeled with [3H]myristic acid, a significant proportion of the label was shown to be specifically incorporated into the protein core of the proteoglycan. Characterization of fatty acyl moiety in the purified proteoglycan by reverse-phase high pressure liquid chromatography revealed that ∼60% of the covalently bound fatty acids was myristate. We further show that this relatively rare 14-carbon fatty acid was bound to the protein core via a hydroxylamine- and alkali-resistant amide bond. The remaining 40% was the more common 16-carbon palmitate, which was bound via a hydroxylamine- and alkali-sensitive thioester bond. Palmitate appeared to be added posttranslationally and derived in part from intracellular elongation of myristate, a process that occurred within the first two hours and was insensitive to inhibition of protein synthesis. Acylation of heparan sulfate proteoglycan represents a novel modification of this gene product and could play a role in a number of biological functions including specific interactions with membrane receptors and ligand stabilization.

Original languageEnglish
Pages (from-to)19980-19989
Number of pages10
JournalJournal of Biological Chemistry
Volume265
Issue number32
Publication statusPublished - Nov 15 1990

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Acylation
Heparan Sulfate Proteoglycans
Myristic Acid
Palmitates
Colon
Fatty Acids
Cells
Carcinoma
Hydroxylamine
Alkalies
Proteoglycans
Proteins
Carbon
Membranes
High pressure liquid chromatography
Protein Transport
Reverse-Phase Chromatography
Amides
Macromolecules
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Biochemistry

Cite this

Iozzo, R. V., Kovalszky, I., Hacobian, N., Schick, P. K., Ellingson, J. S., & Dodge, G. R. (1990). Fatty acylation of heparan sulfate proteoglycan from human colon carcinoma cells. Journal of Biological Chemistry, 265(32), 19980-19989.

Fatty acylation of heparan sulfate proteoglycan from human colon carcinoma cells. / Iozzo, Renato V.; Kovalszky, I.; Hacobian, Nina; Schick, Paul K.; Ellingson, John S.; Dodge, George R.

In: Journal of Biological Chemistry, Vol. 265, No. 32, 15.11.1990, p. 19980-19989.

Research output: Contribution to journalArticle

Iozzo, RV, Kovalszky, I, Hacobian, N, Schick, PK, Ellingson, JS & Dodge, GR 1990, 'Fatty acylation of heparan sulfate proteoglycan from human colon carcinoma cells', Journal of Biological Chemistry, vol. 265, no. 32, pp. 19980-19989.
Iozzo RV, Kovalszky I, Hacobian N, Schick PK, Ellingson JS, Dodge GR. Fatty acylation of heparan sulfate proteoglycan from human colon carcinoma cells. Journal of Biological Chemistry. 1990 Nov 15;265(32):19980-19989.
Iozzo, Renato V. ; Kovalszky, I. ; Hacobian, Nina ; Schick, Paul K. ; Ellingson, John S. ; Dodge, George R. / Fatty acylation of heparan sulfate proteoglycan from human colon carcinoma cells. In: Journal of Biological Chemistry. 1990 ; Vol. 265, No. 32. pp. 19980-19989.
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