Activation of ERK signaling upon alternative protease nexin-1 internalization mediated by syndecan-1

Xiaobiao Li, Joachim Herz, Denis Monard

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Protease nexin-1 (PN-1), an inhibitor of serine proteases, contributes to tissue homeostasis and influences the behavior of some tumor cells. The internalization of PN-1 protease complexes is considered to be mediated by the low-density lipoprotein receptor related protein 1 (LRP1). In this study, both wild-type and LRP1-/- mouse embryonic fibroblasts (MEF) were shown to internalize PN-1. Receptor associated protein (RAP) interfered with PN-1 uptake only in wild-type MEF eel Is, indicating that another receptor mediates PN-1 uptake in the absence of LRP1. In LRP1-/- MEF cells, inhibitor sensitivity and kinetic values (t1/2 at 45 min) of PN-1 uptake showed a similarity to syndecan-1-mediated endocytosis. In these cells, PN-1 uptake was increased by overexpression of full-length syndecan-1 and decreased by RNA interference targeting this proteoglycan. Most important, in contrast to PKA activation known to be triggered by LRP1-mediated internalization, our study shows that syndecan-1-mediated internalization of PN-1 stimulated the Ras-ERK signaling pathway.

Original languageEnglish (US)
Pages (from-to)936-951
Number of pages16
JournalJournal of Cellular Biochemistry
Issue number3
StatePublished - Oct 15 2006


  • ERK signaling
  • Internalization
  • LRP1
  • PN-1
  • Syndecan-1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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