Vascular endothelial growth factor activates STAT proteins in aortic endothelial cells

Manuela Bartoli, Xiaolin Gu, Nai T. Tsai, Richard C Venema, Steven E. Brooks, Mario B Marrero, Ruth B Caldwell

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) intracellular signaling in endothelial cells is initiated by the activation of distinct tyrosine kinase receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1/KDR). Because the tyrosine kinase-dependent transcription factors known as STAT (signal transducers and activators of transcription) proteins are important modulators of cell growth responses induced by other growth factor receptors, we have determined the effects VEGF of on STAT activation in BAEC (bovine aortic endothelial cells). Here, we show that VEGF induces tyrosine phosphorylation and nuclear translocation of STAT1 and STAT6. VEGF also stimulates STAT3 tyrosine phosphorylation, but nuclear translocation does not occur. We found that placenta growth factor, which selectively activates VEGFR1, has no effect on the STATs. However, upon VEGF stimulation, STAT1 associates with the VEGFR2 in a tyrosine kinase-dependent manner, indicating that VEGF-induced STAT1 activation is mediated primarily by VEGFR2. Thus, our study shows for the first time that VEGF activates the STAT pathway through VEGFR2. Because the growth-promoting activity of VEGF depends upon VEGFR2 activation, these findings suggest a role for the STATs in the regulation of gene expression associated with the angiogenic effects of VEGF.

Original languageEnglish (US)
Pages (from-to)33189-33192
Number of pages4
JournalJournal of Biological Chemistry
Volume275
Issue number43
DOIs
StatePublished - Oct 27 2000

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STAT Transcription Factors
Endothelial cells
Vascular Endothelial Growth Factor A
Endothelial Cells
Chemical activation
Phosphorylation
Transcription
Transducers
Protein-Tyrosine Kinases
Tyrosine
Growth Factor Receptors
Gene Expression Regulation
Receptor Protein-Tyrosine Kinases
Cell growth
Gene expression
Modulators
Transcriptional Activation
Intercellular Signaling Peptides and Proteins
Transcription Factors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Vascular endothelial growth factor activates STAT proteins in aortic endothelial cells. / Bartoli, Manuela; Gu, Xiaolin; Tsai, Nai T.; Venema, Richard C; Brooks, Steven E.; Marrero, Mario B; Caldwell, Ruth B.

In: Journal of Biological Chemistry, Vol. 275, No. 43, 27.10.2000, p. 33189-33192.

Research output: Contribution to journalArticle

Bartoli, Manuela ; Gu, Xiaolin ; Tsai, Nai T. ; Venema, Richard C ; Brooks, Steven E. ; Marrero, Mario B ; Caldwell, Ruth B. / Vascular endothelial growth factor activates STAT proteins in aortic endothelial cells. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 43. pp. 33189-33192.
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