Activation of ERK signaling upon alternative protease nexin-1 internalization mediated by syndecan-1.
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. (c) 2006 Wiley-Liss, Inc.[1]References
- Activation of ERK signaling upon alternative protease nexin-1 internalization mediated by syndecan-1. Li, X., Herz, J., Monard, D. J. Cell. Biochem. (2006) [Pubmed]
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