Vascular Endothelial Cell Growth Factor Activates CRE-binding Protein by Signaling through the KDR Receptor Tyrosine Kinase

Lindsey Mayo, Kelly M. Kessler, Roxana Pincheira, Robert S. Warren, David B. Donner

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Vascular endothelial cell growth factor (VEGF) plays a crucial role in the development of the cardiovascular system and in promoting angiogenesis associated with physiological and pathological processes. Although a great deal is known of the cytoplasmic signaling pathways activated by VEGF, much less is known of the mechanisms through which VEGF communicates with the nucleus and alters the activity of transcription factors. Binding of VEGF to the KDR/Flk1 receptor tyrosine kinase induces phosphorylation of the CRE-binding protein (CREB) transcription factor on serine 133 and increases CREB DNA binding and transactivation. p38 MAPK/MSK-1 and protein kinase C/p90RSK pathways mediate CREB phosphorylation. Confocal microscopy shows that VEGF-induced phosphorylation of nuclear CREB is blocked by pharmacological inhibition of protein kinase C and p38 mitogen-activated protein kinase signaling. Thus, KDR/Flk1 uses multiple pathways to transmit signals into the nucleus where CREB becomes activated. These results suggest that CREB may play a role in alterations of gene expression important to angiogenesis.

Original languageEnglish
Pages (from-to)25184-25189
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number27
DOIs
StatePublished - Jul 6 2001

Fingerprint

Vascular Endothelial Growth Factor Receptor-2
Endothelial cells
Receptor Protein-Tyrosine Kinases
Cell growth
Vascular Endothelial Growth Factor A
Intercellular Signaling Peptides and Proteins
Carrier Proteins
Phosphorylation
DNA-Binding Proteins
p38 Mitogen-Activated Protein Kinases
Protein Kinase C
Transcription Factors
Physiological Phenomena
Cardiovascular system
Confocal microscopy
Pathologic Processes
Cardiovascular System
Gene expression
Confocal Microscopy
Serine

ASJC Scopus subject areas

  • Biochemistry

Cite this

Vascular Endothelial Cell Growth Factor Activates CRE-binding Protein by Signaling through the KDR Receptor Tyrosine Kinase. / Mayo, Lindsey; Kessler, Kelly M.; Pincheira, Roxana; Warren, Robert S.; Donner, David B.

In: Journal of Biological Chemistry, Vol. 276, No. 27, 06.07.2001, p. 25184-25189.

Research output: Contribution to journalArticle

Mayo, Lindsey ; Kessler, Kelly M. ; Pincheira, Roxana ; Warren, Robert S. ; Donner, David B. / Vascular Endothelial Cell Growth Factor Activates CRE-binding Protein by Signaling through the KDR Receptor Tyrosine Kinase. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 27. pp. 25184-25189.
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