A potent inhibitor of endothelial cell proliferation is generated by proteolytic cleavage of the chemokine platelet factor 4

Shalley K. Gupta, Tom Hassel, Jai Pal Singh

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Platelet factor 4 (PF-4) is an archetype of the 'chemokine' family of low molecular weight proteins that play an important role in injury responses and inflammation. From activated human leukocyte culture supernatants, we have isolated a form of PF-4 that acts as a potent inhibitor of endothelial cell proliferation. The PF-4 derivative is generated by peptide bond cleavage between Thr-16 and Ser-17, a site located downstream from the highly conserved and structurally important CXC motif. The unique cleavage leads to a loss of one of the structurally important large loops in the PF-4 molecule and generation of an N terminus with basic residues that have the potential to interact with the acidic extracellular domain of the G-protein-coupled chemokine receptor. The N-terminal processed PF-4 exhibited a 30- to 50-fold greater growth inhibitory activity on endothelial cells than PF-4. Since endothelial cell growth inhibition is the only known cellular activity of the cleaved PF-4, we have designated this chemokine endothelial cell growth inhibitor. The N-terminal processing of PF-4 may represent an important mechanism for modulating PF-4 activity on endothelial cells during tissue injury, inflammation, and neoplasia.

Original languageEnglish (US)
Pages (from-to)7799-7803
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number17
DOIs
StatePublished - Aug 15 1995
Externally publishedYes

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Platelet Factor 4
Chemokines
Endothelial Cells
Cell Proliferation
Inflammation
Growth Inhibitors
Chemokine Receptors
Wounds and Injuries
Growth
G-Protein-Coupled Receptors
Leukocytes
Molecular Weight
Peptides

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A potent inhibitor of endothelial cell proliferation is generated by proteolytic cleavage of the chemokine platelet factor 4. / Gupta, Shalley K.; Hassel, Tom; Singh, Jai Pal.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 17, 15.08.1995, p. 7799-7803.

Research output: Contribution to journalArticle

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