help button home button Am J Pathol JNCI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Roberts, D. M.
Right arrow Articles by Bautch, V. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Roberts, D. M.
Right arrow Articles by Bautch, V. L.
(American Journal of Pathology. 2004;164:1531-1535.)
© 2004 American Society for Investigative Pathology

Short Communication

The Vascular Endothelial Growth Factor (VEGF) Receptor Flt-1 (VEGFR-1) Modulates Flk-1 (VEGFR-2) Signaling During Blood Vessel Formation

David M. Roberts*, Joseph B. Kearney*, Jennifer H. Johnson{dagger}, Michael P. Rosenberg{dagger}, Rakesh Kumar{dagger} and Victoria L. Bautch*{ddagger}§

From the Program in Genetics and Molecular Biology,* the Carolina Cardiovascular Biology Center,{ddagger} and the Department of Biology,§ University of North Carolina at Chapel Hill, Chapel Hill; and Glaxo-SmithKline R&D,{dagger} Research Triangle Park, North Carolina

Mice lacking the vascular endothelial growth factor (VEGF) receptor flt-1 (VEGFR-1) die from vascular overgrowth, caused primarily by aberrant endothelial cell division (Kearney JB, Ambler CA, Monaco KA, Johnson N, Rapoport RG, Bautch VL: Vascular endothelial growth factor receptor Flt-1 negatively regulates developmental blood vessel formation by modulating endothelial cell division. Blood 2002, 99:2397–2407). Because a second high-affinity VEGF receptor, flk-1, produces a positive endothelial proliferation signal, it was logical to ask whether flt-1 affects developmental blood vessel formation by modulating signaling through flk-1. Differentiated embryonic stem cell cultures lacking flt-1 (flt-1–/–) had increased flk-1 tyrosine phosphorylation, indicating that flk-1 signaling is up-regulated in the mutant background. The selective flk-1 inhibitor SU5416 partially rescued the flt-1–/– mutant phenotype, and this rescue was accompanied by a decrease in the relative amount of flk-1 tyrosine phosphorylation. Thus reduced flk-1 signal transduction can partially compensate for the lack of flt-1. The flt-1–/– mutant phenotype was also partially rescued by Flt-1/Fc, a truncated flt-1 that binds and sequesters the VEGF ligand. Taken together, these data show that down-regulation of flk-1 signaling by two different strategies partially rescues the developmental vascular overgrowth seen in the absence of flt-1, and they support a model whereby flt-1 modulates the flk-1 signal at an early point in the pathway.




This article has been cited by other articles:


Home page
 J. Cell Biol.Home page
N. C. Kappas, G. Zeng, J. C. Chappell, J. B. Kearney, S. Hazarika, K. G. Kallianos, C. Patterson, B. H. Annex, and V. L. Bautch
The VEGF receptor Flt-1 spatially modulates Flk-1 signaling and blood vessel branching
J. Cell Biol., May 28, 2008; 181(5): 847 - 858.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Soro, A. Orecchia, L. Morbidelli, P. M. Lacal, V. Morea, K. Ballmer-Hofer, F. Ruffini, M. Ziche, S. D'Atri, G. Zambruno, et al.
A proangiogenic peptide derived from vascular endothelial growth factor receptor-1 acts through {alpha}5{beta}1 integrin
Blood, April 1, 2008; 111(7): 3479 - 3488.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
S. Hazarika, A. O. Dokun, Y. Li, A. S. Popel, C. D. Kontos, and B. H. Annex
Impaired Angiogenesis After Hindlimb Ischemia in Type 2 Diabetes Mellitus: Differential Regulation of Vascular Endothelial Growth Factor Receptor 1 and Soluble Vascular Endothelial Growth Factor Receptor 1
Circ. Res., October 26, 2007; 101(9): 948 - 956.
[Abstract] [Full Text] [PDF]

Home page
 J. Dent. Res.Home page
J. Dai and A.B.M. Rabie
VEGF: an Essential Mediator of Both Angiogenesis and Endochondral Ossification
J. Dent. Res., October 1, 2007; 86(10): 937 - 950.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
G. Zeng, S. M. Taylor, J. R. McColm, N. C. Kappas, J. B. Kearney, L. H. Williams, M. E. Hartnett, and V. L. Bautch
Orientation of endothelial cell division is regulated by VEGF signaling during blood vessel formation
Blood, February 15, 2007; 109(4): 1345 - 1352.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Cai, W. G. Jiang, M. B. Grant, and M. Boulton
Pigment Epithelium-derived Factor Inhibits Angiogenesis via Regulated Intracellular Proteolysis of Vascular Endothelial Growth Factor Receptor 1
J. Biol. Chem., February 10, 2006; 281(6): 3604 - 3613.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
R. Summer, D. N. Kotton, S. Liang, K. Fitzsimmons, X. Sun, and A. Fine
Embryonic Lung Side Population Cells Are Hematopoietic and Vascular Precursors
Am. J. Respir. Cell Mol. Biol., July 1, 2005; 33(1): 32 - 40.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
D. M. Roberts, A. L. Anderson, M. Hidaka, R. L. Swetenburg, C. Patterson, W. L. Stanford, and V. L. Bautch
A Vascular Gene Trap Screen Defines RasGRP3 as an Angiogenesis-Regulated Gene Required for the Endothelial Response to Phorbol Esters
Mol. Cell. Biol., December 15, 2004; 24(24): 10515 - 10528.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. B. Kearney, N. C. Kappas, C. Ellerstrom, F. W. DiPaola, and V. L. Bautch
The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular sprout formation and branching morphogenesis
Blood, June 15, 2004; 103(12): 4527 - 4535.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2004 by the American Society for Investigative Pathology.