Cargando…
Involvement of Src kinases and PLCγ2 in clot retraction
The integrin α(IIb)β(3) plays a critical role in mediating clot retraction by platelets which is important in vivo in consolidating thrombus formation. Actin–myosin interaction is essential for clot retraction. In the present study, we demonstrate that the structurally distinct Src kinase inhibitors...
Autores principales: | , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Pergamon Press
2007
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884692/ https://www.ncbi.nlm.nih.gov/pubmed/17055557 http://dx.doi.org/10.1016/j.thromres.2006.09.003 |
_version_ | 1782133606686130176 |
---|---|
author | Suzuki-Inoue, Katsue Hughes, Craig E. Inoue, Osamu Kaneko, Makoto Cuyun-Lira, Olga Takafuta, Toshiro Watson, Steve P. Ozaki, Yukio |
author_facet | Suzuki-Inoue, Katsue Hughes, Craig E. Inoue, Osamu Kaneko, Makoto Cuyun-Lira, Olga Takafuta, Toshiro Watson, Steve P. Ozaki, Yukio |
author_sort | Suzuki-Inoue, Katsue |
collection | PubMed |
description | The integrin α(IIb)β(3) plays a critical role in mediating clot retraction by platelets which is important in vivo in consolidating thrombus formation. Actin–myosin interaction is essential for clot retraction. In the present study, we demonstrate that the structurally distinct Src kinase inhibitors, PP2 and PD173952, significantly reduced the rate of clot retraction, but did not prevent it reaching completion. This effect was accompanied by abolition of α(IIb)β(3)-dependent protein tyrosine phosphorylation, including PLCγ2. A role for PLCγ2 in mediating clot retraction was demonstrated using PLCγ2-deficient murine platelets. Furthermore, platelet adhesion to fibrinogen leads to MLC phosphorylation through a pathway that is inhibited by PP2 and by the PLC inhibitor, U73122. These results demonstrate a partial role for Src kinase-dependent activation of PLCγ2 and MLC phosphorylation in mediating clot retraction downstream of integrin α(IIb)β(3). |
format | Text |
id | pubmed-1884692 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Pergamon Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-18846922007-05-31 Involvement of Src kinases and PLCγ2 in clot retraction Suzuki-Inoue, Katsue Hughes, Craig E. Inoue, Osamu Kaneko, Makoto Cuyun-Lira, Olga Takafuta, Toshiro Watson, Steve P. Ozaki, Yukio Thromb Res Regular Article The integrin α(IIb)β(3) plays a critical role in mediating clot retraction by platelets which is important in vivo in consolidating thrombus formation. Actin–myosin interaction is essential for clot retraction. In the present study, we demonstrate that the structurally distinct Src kinase inhibitors, PP2 and PD173952, significantly reduced the rate of clot retraction, but did not prevent it reaching completion. This effect was accompanied by abolition of α(IIb)β(3)-dependent protein tyrosine phosphorylation, including PLCγ2. A role for PLCγ2 in mediating clot retraction was demonstrated using PLCγ2-deficient murine platelets. Furthermore, platelet adhesion to fibrinogen leads to MLC phosphorylation through a pathway that is inhibited by PP2 and by the PLC inhibitor, U73122. These results demonstrate a partial role for Src kinase-dependent activation of PLCγ2 and MLC phosphorylation in mediating clot retraction downstream of integrin α(IIb)β(3). Pergamon Press 2007 /pmc/articles/PMC1884692/ /pubmed/17055557 http://dx.doi.org/10.1016/j.thromres.2006.09.003 Text en © 2007 Elsevier Ltd. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license |
spellingShingle | Regular Article Suzuki-Inoue, Katsue Hughes, Craig E. Inoue, Osamu Kaneko, Makoto Cuyun-Lira, Olga Takafuta, Toshiro Watson, Steve P. Ozaki, Yukio Involvement of Src kinases and PLCγ2 in clot retraction |
title | Involvement of Src kinases and PLCγ2 in clot retraction |
title_full | Involvement of Src kinases and PLCγ2 in clot retraction |
title_fullStr | Involvement of Src kinases and PLCγ2 in clot retraction |
title_full_unstemmed | Involvement of Src kinases and PLCγ2 in clot retraction |
title_short | Involvement of Src kinases and PLCγ2 in clot retraction |
title_sort | involvement of src kinases and plcγ2 in clot retraction |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884692/ https://www.ncbi.nlm.nih.gov/pubmed/17055557 http://dx.doi.org/10.1016/j.thromres.2006.09.003 |
work_keys_str_mv | AT suzukiinouekatsue involvementofsrckinasesandplcg2inclotretraction AT hughescraige involvementofsrckinasesandplcg2inclotretraction AT inoueosamu involvementofsrckinasesandplcg2inclotretraction AT kanekomakoto involvementofsrckinasesandplcg2inclotretraction AT cuyunliraolga involvementofsrckinasesandplcg2inclotretraction AT takafutatoshiro involvementofsrckinasesandplcg2inclotretraction AT watsonstevep involvementofsrckinasesandplcg2inclotretraction AT ozakiyukio involvementofsrckinasesandplcg2inclotretraction |