Role of thrombospondin-1-derived peptide, 4N1K, in FGF-2-induced angiogenesis

Exp Cell Res. 1999 Nov 1;252(2):262-72. doi: 10.1006/excr.1999.4622.


Angiogenesis involves proliferation of capillary endothelial cells and formation of lumen-containing tube-like structures. A recently established murine brain capillary endothelial cell line, IBE, can either proliferate or form tube-like structures (i.e., differentiate) in response to fibroblast growth factor-2 (FGF-2), dependent on the culture conditions. The 4N1K peptide (KRFYVVMWKK), which is derived from the C-terminal cell-binding domain of thrombospondin-1 (TSP-1), inhibited tube formation, but not proliferation of IBE cells. Polyclonal antibodies against 4N1K blocked TSP-1-induced inhibition of tube formation by IBE cells. 4N1K inhibited tyrosine phosphorylation of focal adhesion kinase and FGF-2-stimulated tyrosine phosphorylation of phospholipase C-gamma in tube-forming, but not proliferating, IBE cells. The peptide also inhibited FGF-2-induced neovascularization in mouse cornea. Our results indicate that TSP-1 may exert its inhibitory effects on angiogenesis via the C-terminal cell-binding domain containing the 4N1K sequence by inhibiting tube formation by endothelial cells.

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / physiology*
  • Fibroblast Growth Factor 2 / pharmacology*
  • Humans
  • Mice
  • Morphogenesis / physiology
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / physiology*
  • Oligopeptides / physiology*
  • Thrombospondin 1 / physiology*


  • 4N1K peptide
  • Oligopeptides
  • Thrombospondin 1
  • Fibroblast Growth Factor 2