Augmented binding and activation of latent transforming growth factor-β by a tryptic fragment of latency associated peptide

M. Abe, N. Oda, Yasufumi Sato, K. Shibata, M. Yamasaki

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Transforming growth factor-β (TGF-β) is secreted in a latent form; thus, activation is critical for the control of TGF-β action. Latent TGF-β exists in a complex in which mature TGF-β is non-covalently linked to latency associated peptide (LAP) and latent TGF-β binding protein (LTBP) complex. We have shown that latent TGF-β is efficiently activated in heterotypic cultures of endothelial cells (ECs) and smooth muscle cells (SMCs). Under those conditions, LAP plays an important role in targeting latent TGF-β to the surface of SMCs, and plasmin and calpain target it to the surface of ECs for activation. Here, we demonstrate in a honiotypic culture system that fragments of LAP increase the binding of latent TGF-β to ECs, resulting in its activation by cell-associated proteolysis. LAP fragments appear to bind to the cell surface and augment the binding of latent TGF-β, independent of transglutaminase. These results suggest a unique mechanism for the activation of latent TGF-β by proteolytic fragments of LAP. The mechanism may arise from degradation by elevated levels of proteases under certain conditions.

Original languageEnglish
Pages (from-to)25-36
Number of pages12
JournalEndothelium: Journal of Endothelial Cell Research
Volume9
Issue number1
DOIs
Publication statusPublished - 2002 Dec 1

Keywords

  • Activation
  • LAP
  • Latent TGF-β
  • Tryptic fragment

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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