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Paxillin is an intrinsic negative regulator of platelet activation in mice
BACKGROUND: Paxillin is a LIM domain protein localized at integrin-mediated focal adhesions. Although paxillin is thought to modulate the functions of integrins, little is known about the contribution of paxillin to signaling pathways in platelets. Here, we studied the role of paxillin in platelet a...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904695/ https://www.ncbi.nlm.nih.gov/pubmed/24383745 http://dx.doi.org/10.1186/1477-9560-12-1 |
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author | Sakata, Asuka Ohmori, Tsukasa Nishimura, Satoshi Suzuki, Hidenori Madoiwa, Seiji Mimuro, Jun Kario, Kazuomi Sakata, Yoichi |
author_facet | Sakata, Asuka Ohmori, Tsukasa Nishimura, Satoshi Suzuki, Hidenori Madoiwa, Seiji Mimuro, Jun Kario, Kazuomi Sakata, Yoichi |
author_sort | Sakata, Asuka |
collection | PubMed |
description | BACKGROUND: Paxillin is a LIM domain protein localized at integrin-mediated focal adhesions. Although paxillin is thought to modulate the functions of integrins, little is known about the contribution of paxillin to signaling pathways in platelets. Here, we studied the role of paxillin in platelet activation in vitro and in vivo. METHODS AND RESULTS: We generated paxillin knockdown (Pxn-KD) platelets in mice by transplanting bone marrow cells transduced with a lentiviral vector carrying a short hairpin RNA sequence, and confirmed that paxillin expression was significantly reduced in platelets derived from the transduced cells. Pxn-KD platelets showed a slight increased in size and augmented integrin αIIbβ3 activation following stimulation of multiple receptors including glycoprotein VI and G protein-coupled receptors. Thromboxane A(2) biosynthesis and the release of α-granules and dense granules in response to agonist stimulation were also enhanced in Pxn-KD platelets. However, Pxn-KD did not increase tyrosine phosphorylation or intracellular calcium mobilization. Intravital imaging confirmed that Pxn-KD enhanced thrombus formation in vivo. CONCLUSIONS: Our findings suggest that paxillin negatively regulates several common platelet signaling pathways, resulting in the activation of integrin αIIbβ3 and release reactions. |
format | Online Article Text |
id | pubmed-3904695 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39046952014-01-29 Paxillin is an intrinsic negative regulator of platelet activation in mice Sakata, Asuka Ohmori, Tsukasa Nishimura, Satoshi Suzuki, Hidenori Madoiwa, Seiji Mimuro, Jun Kario, Kazuomi Sakata, Yoichi Thromb J Original Basic Research BACKGROUND: Paxillin is a LIM domain protein localized at integrin-mediated focal adhesions. Although paxillin is thought to modulate the functions of integrins, little is known about the contribution of paxillin to signaling pathways in platelets. Here, we studied the role of paxillin in platelet activation in vitro and in vivo. METHODS AND RESULTS: We generated paxillin knockdown (Pxn-KD) platelets in mice by transplanting bone marrow cells transduced with a lentiviral vector carrying a short hairpin RNA sequence, and confirmed that paxillin expression was significantly reduced in platelets derived from the transduced cells. Pxn-KD platelets showed a slight increased in size and augmented integrin αIIbβ3 activation following stimulation of multiple receptors including glycoprotein VI and G protein-coupled receptors. Thromboxane A(2) biosynthesis and the release of α-granules and dense granules in response to agonist stimulation were also enhanced in Pxn-KD platelets. However, Pxn-KD did not increase tyrosine phosphorylation or intracellular calcium mobilization. Intravital imaging confirmed that Pxn-KD enhanced thrombus formation in vivo. CONCLUSIONS: Our findings suggest that paxillin negatively regulates several common platelet signaling pathways, resulting in the activation of integrin αIIbβ3 and release reactions. BioMed Central 2014-01-02 /pmc/articles/PMC3904695/ /pubmed/24383745 http://dx.doi.org/10.1186/1477-9560-12-1 Text en Copyright © 2014 Sakata et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Original Basic Research Sakata, Asuka Ohmori, Tsukasa Nishimura, Satoshi Suzuki, Hidenori Madoiwa, Seiji Mimuro, Jun Kario, Kazuomi Sakata, Yoichi Paxillin is an intrinsic negative regulator of platelet activation in mice |
title | Paxillin is an intrinsic negative regulator of platelet activation in mice |
title_full | Paxillin is an intrinsic negative regulator of platelet activation in mice |
title_fullStr | Paxillin is an intrinsic negative regulator of platelet activation in mice |
title_full_unstemmed | Paxillin is an intrinsic negative regulator of platelet activation in mice |
title_short | Paxillin is an intrinsic negative regulator of platelet activation in mice |
title_sort | paxillin is an intrinsic negative regulator of platelet activation in mice |
topic | Original Basic Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904695/ https://www.ncbi.nlm.nih.gov/pubmed/24383745 http://dx.doi.org/10.1186/1477-9560-12-1 |
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