Linked Life Data

18987193

Source:http://linkedlifedata.com/resource/pubmed/id/18987193

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
2008-11-6
pubmed:abstractText
Low-density lipoprotein receptor-related protein (LRP-1) is an endocytic receptor for diverse proteins, including matrix metalloproteinase-9 (MMP-9), and a cell-signaling receptor. In the peripheral nervous system (PNS), LRP-1 is robustly expressed by Schwann cells only after injury. Herein, we demonstrate that MMP-9 activates extracellular-signal-regulated kinase (ERK1/2) and Akt in Schwann cells in culture. MMP-9 also promotes Schwann cell migration. These activities require LRP-1. MMP-9-induced cell signaling and migration were blocked by inhibiting MMP-9-binding to LRP-1 with receptor-associated protein (RAP) or by LRP-1 gene silencing. The effects of MMP-9 on Schwann cell migration also were inhibited by blocking the cell-signaling response. An antibody targeting the hemopexin domain of MMP-9, which mediates the interaction with LRP-1, blocked MMP-9-induced cell signaling and migration. Furthermore, a novel glutathione-S-transferase fusion protein (MMP-9-PEX), which includes only the hemopexin domain of MMP-9, replicated the activities of intact MMP-9, activating Schwann cell signaling and migration by an LRP-1-dependent pathway. Constitutively active MEK1 promoted Schwann cell migration; in these cells, MMP-9-PEX had no further effect, indicating that ERK1/2 activation is sufficient to explain the effects of MMP-9-PEX on Schwann cell migration. Injection of MMP-9-PEX into sciatic nerves, 24 h after crush injury, robustly increased phosphorylation of ERK1/2 and Akt. This response was inhibited by RAP. MMP-9-PEX failed to activate cell signaling in uninjured nerves, consistent with the observation that Schwann cells express LRP-1 at significant levels only after nerve injury. These results establish LRP-1 as a cell-signaling receptor for MMP-9, which may be significant in regulating Schwann cell migration and physiology in PNS injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11571-82
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18987193-Animals, pubmed-meshheading:18987193-Animals, Newborn, pubmed-meshheading:18987193-Cell Death, pubmed-meshheading:18987193-Cell Movement, pubmed-meshheading:18987193-Cells, Cultured, pubmed-meshheading:18987193-Drug Interactions, pubmed-meshheading:18987193-Enzyme Inhibitors, pubmed-meshheading:18987193-Gene Expression Regulation, pubmed-meshheading:18987193-Hemopexin, pubmed-meshheading:18987193-LDL-Receptor Related Protein-Associated Protein, pubmed-meshheading:18987193-Matrix Metalloproteinase 9, pubmed-meshheading:18987193-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:18987193-Neuregulin-1, pubmed-meshheading:18987193-Oncogene Protein v-akt, pubmed-meshheading:18987193-Protein Interaction Domains and Motifs, pubmed-meshheading:18987193-RNA, Small Interfering, pubmed-meshheading:18987193-Rats, pubmed-meshheading:18987193-Schwann Cells, pubmed-meshheading:18987193-Sciatic Nerve, pubmed-meshheading:18987193-Sciatic Neuropathy, pubmed-meshheading:18987193-Signal Transduction, pubmed-meshheading:18987193-rap GTP-Binding Proteins
pubmed:year
2008
pubmed:articleTitle
The hemopexin domain of matrix metalloproteinase-9 activates cell signaling and promotes migration of schwann cells by binding to low-density lipoprotein receptor-related protein.
pubmed:affiliation
Department of Anesthesiology and Pathology, University of California, San Diego, La Jolla, California 92093-0629, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural