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Src kinase phosphor...
Src kinase phosphorylates vascular endothelial-cadherin in response to vascular endothelial growth factor : identification of tyrosine 685 as the unique target site
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Wallez, Y. (författare)
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Cand, F. (författare)
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Cruzalegui, F. (författare)
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- Wernstedt, Christer (författare)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Souchelnytskyi, Serhiy (författare)
- Karolinska Institutet,Uppsala universitet,Ludwiginstitutet för cancerforskning
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Vilgrain, I. (författare)
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Huber, P. (författare)
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(creator_code:org_t)
- 2006-08-14
- 2007
- Engelska.
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 26:7, s. 1067-1077
- Relaterad länk:
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Src-family tyrosine kinases are regulatory proteins that play a pivotal role in the disorganization of cadherin-dependent cell-cell contacts. We previously showed that Src was associated with vascular endothelial (VE)-cadherin and that tyrosine phosphorylation level of VE-cadherin was dramatically increased in angiogenic tissues as compared to quiescent tissues. Here, we examined whether VE-cadherin was a direct substrate for Src in vascular endothelial growth factor (VEGF)-induced VE-cadherin phosphorylation, and we identified the target tyrosine sites. Co-transfections of Chinese hamster ovary cells (CHO) cells with VE-cadherin and constitutively active Src (Y530F) resulted in a robust tyrosine phosphorylation of VE-cadherin that was not detected with kinase-dead Src (K298M). In an in vitro Src assay, the VE-cadherin cytoplasmic domain is directly phosphorylated by purified Src as well as the tyrosine residue 685 (Tyr)685-containing peptide RPSLY(685)AQVQ. VE-cadherin peptide mapping from human umbilical vein endothelial cells stimulated by VEGF and VE-cadherin-CHO cells transfected with active Src revealed that Y685 was the unique phosphorylated site. The presence of PhosphoY685 was confirmed by its ability to bind to C-terminal Src kinase-SH2 domain in a pull-down assay. Finally, we found that in a VEGF-induced wound-healing assay, cadherin adhesive activity was impaired by Src kinase inhibitors. These data identify that VEGF-induced-VE-cadherin tyrosine phosphorylation is mediated by Src on Y685, a process that appears to be critical for VEGF-induced endothelial cell migration.
Nyckelord
- Adherens junctions
- Angiogenesis
- Tyrosine kinases
- VE-cadherin
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Oncogene
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