Evidence map›Paper›PMID 24129569›Full record

ArticleThe Journal of biological chemistry2013

LRP1 assembles unique co-receptor systems to initiate cell signaling in response to tissue-type plasminogen activator and myelin-associated glycoprotein.

Elisabetta Mantuano, Michael S Lam, Steven L Gonias

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 84 citations in OpenAlex.

  1. Article
  2. Intracellular Signaling Regulated by Activated αInternational journal of molecular sciences · 2026
    Review
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  16. α1-Antitrypsin derived SP16 peptide demonstrates efficacy in rodent models of acute and neuropathic pain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  17. A Soluble PrPJournal of immunology (Baltimore, Md. : 1950) · 2022
    Article
  18. Article
  19. Article
  20. Review

4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Elisabetta MantuanoDepartment of Pathology, University of California San Diego School of Medicine, La Jolla, California 92093.
Michael S LamDepartment of Pathology, University of California San Diego School of Medicine, La Jolla, California 92093.
Steven L GoniasDepartment of Pathology, University of California San Diego School of Medicine, La Jolla, California 92093. Electronic address: sgonias@ucsd.edu.
University of California, San Diego · US

Funding

REGULATION OF UROKINASE RECEPTOR ACTIVITY BY LRPR01HL060551 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GONIAS, STEVEN L. · 1999 to 2014
$4.0M
Alpha2-macroglobulin in peripheral nerve injuryR01NS054671 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GONIAS, STEVEN L. · 2007 to 2011
$1.7M
NHLBI NIH HHS HL-060551NHLBI NIH HHS R01 HL060551NINDS NIH HHS NS-054671NINDS NIH HHS R01 NS054671
6 · The paper itself

Abstract

In addition to functioning as an activator of fibrinolysis, tissue-type plasminogen activator (tPA) interacts with neurons and regulates multiple aspects of neuronal cell physiology. In this study, we examined the mechanism by which tPA initiates cell signaling in PC12 and N2a neuron-like cells. We demonstrate that enzymatically active and inactive tPA (EI-tPA) activate ERK1/2 in a biphasic manner. Rapid ERK1/2 activation is dependent on LDL receptor-related protein-1 (LRP1). In the second phase, ERK1/2 is activated by tPA independently of LRP1. The length of the LRP1-dependent phase varied inversely with the tPA concentration. Rapid ERK1/2 activation in response to EI-tPA and activated α2-macroglobulin (α2M*) required the NMDA receptor and Trk receptors, which assemble with LRP1 into a single pathway. Assembly of this signaling system may have been facilitated by the bifunctional adapter protein, PSD-95, which associated with LRP1 selectively in cells treated with EI-tPA or α2M*. Myelin-associated glycoprotein binds to LRP1 with high affinity but failed to induce phosphorylation of TrkA or ERK1/2. Instead, myelin-associated glycoprotein recruited p75 neurotrophin receptor (p75NTR) into a complex with LRP1 and activated RhoA. p75NTR was not recruited by other LRP1 ligands, including EI-tPA and α2M*. Lactoferrin functioned as an LRP1 signaling antagonist, inhibiting Trk receptor phosphorylation and ERK1/2 activation in response to EI-tPA. These results demonstrate that LRP1-initiated cell signaling is ligand-dependent. Proteins that activate cell signaling by binding to LRP1 assemble different co-receptor systems. Ligand-specific co-receptor recruitment provides a mechanism by which one receptor, LRP1, may trigger different signaling responses.

Indexed as

alpha-MacroglobulinsAnimalsDisks Large Homolog 4 ProteinGuanylate KinasesHumansIntracellular Signaling Peptides and ProteinsLactoferrinLow Density Lipoprotein Receptor-Related Protein-1MAP Kinase Signaling SystemMembrane ProteinsMiceMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Myelin-Associated GlycoproteinNerve Tissue ProteinsPC12 Cellsalpha-MacroglobulinsDisks Large Homolog 4 ProteinDLG4 protein, humanDlg4 protein, mouseDlg4 protein, ratGuanylate KinasesIntracellular Signaling Peptides and ProteinsLactoferrinLow Density Lipoprotein Receptor-Related Protein-1LRP1 protein, humanLrp1 protein, mouseLtf protein, mouseMAG protein, humanMag protein, mouseMAPK1 protein, humanMembrane ProteinsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Myelin-Associated GlycoproteinNerve Tissue ProteinsNGFR protein, humanNgfr protein, mouseNgfr protein, ratReceptors, Growth FactorReceptors, LDLReceptors, Nerve Growth FactorTissue Plasminogen ActivatorTumor Suppressor ProteinsCell SignalingERKLipoprotein-like Receptor (LRP)Protease InhibitorTissue-type Plasminogen Activator (tPA)

Identifiers

PMID24129569
PMCPMC3837140
OpenAlexW2077976088

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.