Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Myc-dependent endothelial proliferation is controlled by phosphotyrosine 1212 in VEGF receptor-2
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
Show others and affiliations
2019 (English)In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 20, no 11, article id e47845Article in journal (Refereed) Published
Abstract [en]

Exaggerated signaling by vascular endothelial growth factor (VEGF)-A and its receptor, VEGFR2, in pathologies results in poor vessel function. Still, pharmacological suppression of VEGFA/VEGFR2 may aggravate disease. Delineating VEGFR2 signaling in vivo provides strategies for suppression of specific VEGFR2-induced pathways. Three VEGFR2 tyrosine residues (Y949, Y1212, and Y1173) induce downstream signaling. Here, we show that knock-in of phenylalanine to create VEGFR2 Y1212F in C57Bl/6 and FVB mouse strains leads to loss of growth factor receptor-bound protein 2- and phosphoinositide 3 '-kinase (PI3K)p85 signaling. C57Bl/6 Vegfr2(Y1212F/Y1212F) show reduced embryonic endothelial cell (EC) proliferation and partial lethality. FVB Vegfr2(Y1212F/Y1212F) show reduced postnatal EC proliferation. Reduced EC proliferation in Vegfr2(Y1212F/Y1212F) explants is rescued by c-Myc overexpression. We conclude that VEGFR2 Y1212 signaling induces activation of extracellular-signal-regulated kinase (ERK)1/2 and Akt pathways required for c-Myc-dependent gene regulation, endothelial proliferation, and vessel stability.

Place, publisher, year, edition, pages
2019. Vol. 20, no 11, article id e47845
Keywords [en]
angiogenesis, GRB2, Nck, PI3Kp85, proliferation
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-397954DOI: 10.15252/embr.201947845ISI: 000496229500001PubMedID: 31545012OAI: oai:DiVA.org:uu-397954DiVA, id: diva2:1382267
Funder
Swedish Research Council, 2015-02375Swedish Cancer Society, CAN2016/578Knut and Alice Wallenberg Foundation, KAW 2015.0030Knut and Alice Wallenberg Foundation, 2015.0275Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-01-02Bibliographically approved

Open Access in DiVA

fulltext(5379 kB)8 downloads
File information
File name FULLTEXT01.pdfFile size 5379 kBChecksum SHA-512
3ae47ba0276e1dfe62021d6f5d5055ac7a00dd0ca42e173c6d4afe5ddc75bf01821f4f7bc80de3bfd89468af1db5f283556490a2de80122e7266aca7ec06d4c6
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Testini, ChiaraSmith, Ross O.Jin, YiMartinsson, PernillaSun, YingHedlund, MarieSainz-Jaspeado, MiguelHellström, MatsClaesson-Welsh, Lena
By organisation
Science for Life Laboratory, SciLifeLabVascular BiologyExperimental and Clinical Oncology
In the same journal
EMBO Reports
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 8 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 6 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf