Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Special issues
    • Subject collections
    • Interviews
    • Sign up for alerts
  • About us
    • About JCS
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Workshops and Meetings
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • JCS Prize
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contact
    • Contact the journal
    • Subscriptions
    • Advertising
    • Feedback
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

User menu

  • Log in

Search

  • Advanced search
Journal of Cell Science
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

supporting biologistsinspiring biology

Journal of Cell Science

  • Log in
Advanced search

RSS   Twitter  Facebook   YouTube  

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Special issues
    • Subject collections
    • Interviews
    • Sign up for alerts
  • About us
    • About JCS
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Workshops and Meetings
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • JCS Prize
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contact
    • Contact the journal
    • Subscriptions
    • Advertising
    • Feedback
Accepted Manuscript
Research Article
PAI1 blocks effects of tissue-type plasminogen activator on cell-signaling and physiology mediated by the NMDA receptor
Steven L. Gonias, Michael A. Banki, Andrew S. Gilder, Pardis Azmoon, Wendy M. Campana, Elisabetta Mantuano
J Cell Sci 2018 : jcs.217083 doi: 10.1242/jcs.217083 Published 21 June 2018
Steven L. Gonias
Department of Pathology, University of California San Diego, La Jolla CA, 92093, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Steven L. Gonias
  • For correspondence: sgonias@ucsd.edu
Michael A. Banki
Department of Pathology, University of California San Diego, La Jolla CA, 92093, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew S. Gilder
Department of Pathology, University of California San Diego, La Jolla CA, 92093, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pardis Azmoon
Department of Pathology, University of California San Diego, La Jolla CA, 92093, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wendy M. Campana
Department of Anesthesiology and the Program in Neuroscience, University of California San Diego, La Jolla CA, 92093, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elisabetta Mantuano
Department of Pathology, University of California San Diego, La Jolla CA, 92093, USADepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & metrics
  • PDF
Loading

Abstract

The fibrinolysis proteinase, tissue-type plasminogen activator (tPA), triggers cell-signaling and regulates cell physiology. In PC12 cells, Schwann cells, and macrophages, the N-methyl-D-aspartate receptor (NMDA-R) mediates tPA-signaling. Plasminogen activator Inhibitor-1 (PAI1) is a rapid inhibitor of tPA enzyme activity. Although tPA-initiated cell-signaling is not dependent on its enzyme active site, we show that tPA-signaling is neutralized by PAI1. In PC12 cells, PAI1 blocked ERK1/2 activation by tPA and neurite outgrowth. In Schwann cells, PAI1 blocked tPA-mediated ERK1/2 activation and cell migration. In macrophages, PAI1 blocked the ability of tPA to inhibit IκBα phosphorylation and cytokine expression. The cell-signaling activity of tPA-PAI1 complex was rescued by forming the complex with PAI1R76→E, which binds to LRP1 with decreased affinity, by pre-treating cells with the LRP1 antagonist, Receptor-associated Protein, or by LRP1 gene-silencing. The inhibitory activity of LRP1 in tPA-PAI1 complex-initiated cell-signaling was unanticipated given the reported role of LRP1 as an NMDA-R co-receptor in signaling responses elicited by free tPA or α2-macroglobulin. We conclude that PAI1 functions as an inhibitor not only of the enzyme activity of tPA but also tPA receptor-mediated activities.

  • Received February 21, 2018.
  • Accepted May 29, 2018.
  • © 2018. Published by The Company of Biologists Ltd
http://www.biologists.com/user-licence-1-1/
Next Article
Back to top
Next Article

Latest complete issue

Keywords

  • Tissue-type plasminogen activator
  • Plasminogen activator inhibitor-1
  • NMDA receptor
  • LDL receptor-related protein-1/LRP1
  • Fibrinolysis
  • Cell-signaling

 Download PDF

Email

Thank you for your interest in spreading the word on Journal of Cell Science.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
PAI1 blocks effects of tissue-type plasminogen activator on cell-signaling and physiology mediated by the NMDA receptor
(Your Name) has sent you a message from Journal of Cell Science
(Your Name) thought you would like to see the Journal of Cell Science web site.
Share
Accepted Manuscript
Research Article
PAI1 blocks effects of tissue-type plasminogen activator on cell-signaling and physiology mediated by the NMDA receptor
Steven L. Gonias, Michael A. Banki, Andrew S. Gilder, Pardis Azmoon, Wendy M. Campana, Elisabetta Mantuano
J Cell Sci 2018 : jcs.217083 doi: 10.1242/jcs.217083 Published 21 June 2018
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Accepted Manuscript
Research Article
PAI1 blocks effects of tissue-type plasminogen activator on cell-signaling and physiology mediated by the NMDA receptor
Steven L. Gonias, Michael A. Banki, Andrew S. Gilder, Pardis Azmoon, Wendy M. Campana, Elisabetta Mantuano
J Cell Sci 2018 : jcs.217083 doi: 10.1242/jcs.217083 Published 21 June 2018

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Alerts

Please log in to add an alert for this article.

Sign in to email alerts with your email address

Article navigation

  • Top
  • Article
  • Info & metrics
  • PDF

Related articles

Cited by...

More in this TOC section

  • BBS4 is required for intraflagellar transport coordination and basal body number in mammalian olfactory cilia
  • A conserved retromer-independent function for RAB-6.2 in C. elegans epidermis integrity
  • An essential role for dNTP homeostasis following CDK-induced replication stress
Show more RESEARCH ARTICLE

Similar articles

Other journals from The Company of Biologists

Development

Journal of Experimental Biology

Disease Models & Mechanisms

Biology Open

Advertisement

Cell scientists to watch – Gloria Brar and Elçin Ünal

Elçin Ünal (left) and Gloria Brar

“…it is important for you as an individual scientist to find the best system to address your specific questions and also to look for synergies outside your own talents and knowledge base.”

Gloria Brar is Assistant Professor of Cell and Developmental Biology and Elçin Ünal is Assistant Professor of Genetics, Genomics and Development. They tell us about running complementary labs at UC Berkeley investigating yeast.

Catch up with early-career first authors in our First Person interviews. Recently, we spoke to Norbert Volkmar and Priyanka Kothari.


Editorial - New Editor on Journal of Cell Science

Asifa Akhtar

We are very pleased to welcome Asifa Akhtar as an Editor of Journal of Cell Science. Asifa’s expertise covers molecular aspects of the nucleus. Our Editor in Chief Michael Way gives the highlights of her career, filled with outstanding scientific achievements.


Cell science at a glance - Linear ubiquitination at a glance

Part of Linear ubiquitination at a glance poster

Linear ubiquitin chains are crucial modulators of innate and adaptive immune responses that act by regulating inflammatory and cell death signalling. Maureen Spit, Eva Rieser and Henning Walczak put together this poster to explain it.


Review  - Lysosomal storage disorders – challenges, concepts and avenues for therapy: beyond rare diseases

Part of Overview of the mechanisms regulating lysosome function: the master regulator TFEB and new players in the field

André Marques and Paul Saftig review the current knowledge on the cellular processes involved in lysosomal storage disorders and discuss how understanding of these rare disorders could be applied to more common diseases.


JCS Meeting – Cell dynamics: organelle-cytoskeleton interface

The second in our series of cell dynamics meetings now turns to organelles. This May 2019 meeting in Lisbon, Portugal, aims to bring together scientists studying the interface between organelles and the cytoskeleton at different scales and perspectives using a range of model systems. Find out more and apply for your place here. The deadline to apply is 15 February.


Call for papers - Cell Biology of the Immune System

Call for papers - Cell Biology of the Immune System

Journal of Cell Science is pleased to welcome submissions for an upcoming special issue on 'Cell Biology of the Immune System' edited by Ana-Maria Lennon-Duménil. We invite you to showcase your breakthrough research on all aspects of cell biology as it relates to the immune system. The articles within this issue will receive extensive exposure to a broad audience of cell biologists and immunologists. Submission deadline: 30 June 2019.


Journal news - New manuscript transfer option

Journal of Cell Science, Journal of Cell Biology and Molecular Biology of the Cell have announced a new manuscript transfer option, which will be available in the first quarter of 2019. It will empower authors whose manuscripts have been declined to seamlessly transfer their manuscripts and associated peer review reports between the journals. 


preLights – A complex containing lysine-acetylated actin inhibits the formin INF2

preLighter Laura McCormick

Laura McCormick highlights a recent preprint from Henry Higgs and team which uses some old-school biochemistry techniques to identify a cellular factor that facilitates INF2 auto-inhibition.


Articles of interest in our sister journals

IMP regulates Kuzbanian to control the timing of Notch signalling in Drosophila follicle cells
Weronika Fic, Celia Faria, Daniel St Johnston
Development 2019 146: dev168963

Hippo signaling promotes lung epithelial lineage commitment by curbing Fgf10 and β-catenin signaling
Thomas Volckaert, Tingting Yuan, Jie Yuan, Eistine Boateng, Seantel Hopkins, Jin-San Zhang, Victor J. Thannickal, Reinhard Fässler, Stijn P. De Langhe
Development 2019 146: dev166454

Articles

  • Accepted manuscripts
  • Issue in progress
  • Latest complete issue
  • Issue archive
  • Archive by article type
  • Special issues
  • Subject collections
  • Interviews
  • Sign up for alerts

About us

  • About Journal of Cell Science
  • Editors and Board
  • Editor biographies
  • Travelling Fellowships
  • Grants and funding
  • Workshops and Meetings
  • The Company of Biologists

For Authors

  • Submit a manuscript
  • Aims and scope
  • Presubmission enquiries
  • Article types
  • Manuscript preparation
  • Cover suggestions
  • Editorial process
  • Promoting your paper
  • Open Access
  • JCS Prize
  • Biology Open transfer

Journal Info

  • Journal policies
  • Rights and permissions
  • Media policies
  • Reviewer guide
  • Sign up for alerts

Contact

  • Contact Journal of Cell Science
  • Subscriptions
  • Advertising
  • Feedback

Twitter   YouTube   LinkedIn

© 2019   The Company of Biologists Ltd   Registered Charity 277992