Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2.
The fibroblast growth factor (FGF) system plays a critical role in the maintenance of vascular integrity via enhancing the stability of VE-cadherin at adherens junctions. However, the precise molecular mechanism is not well understood. In the present study, we aimed to investigate the detailed mecha...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3358251?pdf=render |
| _version_ | 1818298662425460736 |
|---|---|
| author | Kunihiko Hatanaka Anthony A Lanahan Masahiro Murakami Michael Simons |
| author_facet | Kunihiko Hatanaka Anthony A Lanahan Masahiro Murakami Michael Simons |
| author_sort | Kunihiko Hatanaka |
| collection | DOAJ |
| description | The fibroblast growth factor (FGF) system plays a critical role in the maintenance of vascular integrity via enhancing the stability of VE-cadherin at adherens junctions. However, the precise molecular mechanism is not well understood. In the present study, we aimed to investigate the detailed mechanism of FGF regulation of VE-cadherin function that leads to endothelial junction stabilization.In vitro studies demonstrated that the loss of FGF signaling disrupts the VE-cadherin-catenin complex at adherens junctions by increasing tyrosine phosphorylation levels of VE-cadherin. Among protein tyrosine phosphatases (PTPs) known to be involved in the maintenance of the VE-cadherin complex, suppression of FGF signaling reduces SHP2 expression levels and SHP2/VE-cadherin interaction due to accelerated SHP2 protein degradation. Increased endothelial permeability caused by FGF signaling inhibition was rescued by SHP2 overexpression, indicating the critical role of SHP2 in the maintenance of endothelial junction integrity.These results identify FGF-dependent maintenance of SHP2 as an important new mechanism controlling the extent of VE-cadherin tyrosine phosphorylation, thereby regulating its presence in adherens junctions and endothelial permeability. |
| first_indexed | 2024-12-13T04:38:53Z |
| format | Article |
| id | doaj.art-0342f530be7f4910bfca8726f07f38f6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T04:38:53Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0342f530be7f4910bfca8726f07f38f62022-12-21T23:59:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3760010.1371/journal.pone.0037600Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2.Kunihiko HatanakaAnthony A LanahanMasahiro MurakamiMichael SimonsThe fibroblast growth factor (FGF) system plays a critical role in the maintenance of vascular integrity via enhancing the stability of VE-cadherin at adherens junctions. However, the precise molecular mechanism is not well understood. In the present study, we aimed to investigate the detailed mechanism of FGF regulation of VE-cadherin function that leads to endothelial junction stabilization.In vitro studies demonstrated that the loss of FGF signaling disrupts the VE-cadherin-catenin complex at adherens junctions by increasing tyrosine phosphorylation levels of VE-cadherin. Among protein tyrosine phosphatases (PTPs) known to be involved in the maintenance of the VE-cadherin complex, suppression of FGF signaling reduces SHP2 expression levels and SHP2/VE-cadherin interaction due to accelerated SHP2 protein degradation. Increased endothelial permeability caused by FGF signaling inhibition was rescued by SHP2 overexpression, indicating the critical role of SHP2 in the maintenance of endothelial junction integrity.These results identify FGF-dependent maintenance of SHP2 as an important new mechanism controlling the extent of VE-cadherin tyrosine phosphorylation, thereby regulating its presence in adherens junctions and endothelial permeability.http://europepmc.org/articles/PMC3358251?pdf=render |
| spellingShingle | Kunihiko Hatanaka Anthony A Lanahan Masahiro Murakami Michael Simons Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2. PLoS ONE |
| title | Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2. |
| title_full | Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2. |
| title_fullStr | Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2. |
| title_full_unstemmed | Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2. |
| title_short | Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2. |
| title_sort | fibroblast growth factor signaling potentiates ve cadherin stability at adherens junctions by regulating shp2 |
| url | http://europepmc.org/articles/PMC3358251?pdf=render |
| work_keys_str_mv | AT kunihikohatanaka fibroblastgrowthfactorsignalingpotentiatesvecadherinstabilityatadherensjunctionsbyregulatingshp2 AT anthonyalanahan fibroblastgrowthfactorsignalingpotentiatesvecadherinstabilityatadherensjunctionsbyregulatingshp2 AT masahiromurakami fibroblastgrowthfactorsignalingpotentiatesvecadherinstabilityatadherensjunctionsbyregulatingshp2 AT michaelsimons fibroblastgrowthfactorsignalingpotentiatesvecadherinstabilityatadherensjunctionsbyregulatingshp2 |