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

✍ Scribed by Xiaobiao Li; Joachim Herz; Denis Monard

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 475 KB
• Volume: 99
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20881

✦ Synopsis

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 cells, indicating that another receptor mediates PN‐1 uptake in the absence of LRP1. In LRP1−/− MEF cells, inhibitor sensitivity and kinetic values (t~1/2~ 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. J. Cell. Biochem. 99: 936–951, 2006. © 2006 Wiley‐Liss, Inc.