Abstract
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 language | English (US) |
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Pages (from-to) | 936-951 |
Number of pages | 16 |
Journal | Journal of Cellular Biochemistry |
Volume | 99 |
Issue number | 3 |
DOIs | |
State | Published - Oct 15 2006 |
Keywords
- ERK signaling
- Internalization
- LRP1
- PN-1
- Syndecan-1
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology