The anti-HIV cytokine midkine binds the cell surface-expressed nucleolin as a low affinity receptor

Elias A. Said, Bernard Krust, Sébastien Nisole, Josette Svab, Jean Paul Briand, Ara G. Hovanessian

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

The growth factor midkine (MK) is a cytokine that inhibits the attachment of human immunodeficiency virus particles by a mechanism similar to the nucleolin binding HB-19 pseudopeptide. Here we show that the binding of MK to cells occurs specifically at a high and a low affinity binding site. HB-19 prevents the binding of MK to the low affinity binding site only. Confocal immunofluorescence laser microscopy revealed the colocalization of MK and the cell-surface-expressed nucleolin at distinct spots. The use of various deletion constructs of nucleolin then indicated that the extreme C-terminal end of nucleolin, containing repeats of the amino acid motif RGG, is the domain that binds MK. The specific binding of MK to cells is independent of heparan sulfate and chondroitin sulfate expression. After binding to cells, MK enters cells by an active process. Interestingly, the cross-linking of surface-bound MK with a specific antibody results in the clustering of surface nucleolin along with glycosylphosphatidylinositol-linked proteins CD90 and CD59, thus, pointing out that MK binding induces lateral assemblies of nucleolin with specific membrane components of lipid rafts. Our results suggest that the cell surface-expressed nucleolin serves as a low affinity receptor for MK and could be implicated in its entry process.

Original languageEnglish
Pages (from-to)37492-37502
Number of pages11
JournalJournal of Biological Chemistry
Volume277
Issue number40
DOIs
Publication statusPublished - Oct 4 2002

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HIV
Cytokines
Confocal Microscopy
GPI-Linked Proteins
Binding Sites
nucleolin
midkine
Amino Acid Motifs
Heparitin Sulfate
Chondroitin Sulfates
Membrane Lipids
Viruses
Fluorescence Microscopy
Virion
Cluster Analysis
Intercellular Signaling Peptides and Proteins
Microscopic examination
Membranes
Lipids
Amino Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

The anti-HIV cytokine midkine binds the cell surface-expressed nucleolin as a low affinity receptor. / Said, Elias A.; Krust, Bernard; Nisole, Sébastien; Svab, Josette; Briand, Jean Paul; Hovanessian, Ara G.

In: Journal of Biological Chemistry, Vol. 277, No. 40, 04.10.2002, p. 37492-37502.

Research output: Contribution to journalArticle

Said, Elias A. ; Krust, Bernard ; Nisole, Sébastien ; Svab, Josette ; Briand, Jean Paul ; Hovanessian, Ara G. / The anti-HIV cytokine midkine binds the cell surface-expressed nucleolin as a low affinity receptor. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 40. pp. 37492-37502.
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