Thrombospondin-1 affects phosphorylation of far and paxillin- opposite effects on endothelial and smooth muscle cells

L. Iruela-Arispe*, J. L. Alonso

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Thrombospondin-1 (TSP1) has been implicated in the negative regulation of angiogenesis. We are interested in understanding the cellular and molecular mechanisms by which TSP1 mediates this effect. One of the reported functions of TSP1 on endothelial cells is the disruption of focal adhesions. Several signaling pathways that led to proliferation, survival -or avoidance of apoptosis, and migration are linked to the activation of integrals and phosphorylation of intracellular proteins associated with focal adhesions. We sought to investigate the effect of TSP1 on the phosphorylation of two proteins associated with focal adhesions: pp125FAK and paxillin. Experiments were performed on bovine aortic endothelial cells, human microvascular endothelial cells (HMEC), and human smooth muscle cells (HSM). Cells were plated on fibronectin, TSP1, vitronectin, type I collagen, or on fibronectin in the presence of soluble TSP1. We found that when plated on TSP1, cells phosphorylate FAK at negligible levels. Furthermore, when present in a soluble form, TSP1 inhibits FAK phosphorylation on HDMEC platted on fibronectin. The effect is dose-dependent and endothelial cell specific, since it is not seen on HSMC. The region of TSP1 responsible for this effect was mapped by experiments using synthetic peptides. In summary our results demonstrate, at least partially, that TSP1 affects phosphorylation of focal adhesions and revealed that the intracellular pathway associated with this signaling targets FAK kinase and paxillin directly.

Original languageEnglish (US)
Pages (from-to)A1001
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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