Abstract

Angiogenesis is an essential process not only in normal development, but in pathological conditions such as tumor growth and metastasis. New and improved methods for preventing angiogenesis require an understanding of the mechanisms that regulate angiogenesis. Vascular endothelial growth factor (VEGF) and its receptors (VEGFR-lIFlt-l and VEGFR-2/Flk-1/KDR) are considered to be primary regulators of tumor-induced angiogenesis. Activation of VEGFR-2 stimulates angiogenesis, while VEGFR- 1 activation appears to play a dual function by either stimulating angiogenesis or suppressing angiogenesis. Therefore, understanding the molecular mechanisms underlying these strikingly different effects is essential for development of targeted therapeutic interventions aimed at angiogenesis suppression. The overall goal of this proposal is to investigate the mechanism by which VEGFRS are activated and to exploit these differences to suppress angiogenesis. This proposal focuses on the mechanism by which ligand binding results in the activation of VEGF receptors, a fundamental issue in signal transduction and angiogenesis. Once we determine the mechanism by which VEGF receptors are engaged it will be possible to attenuate the angiogenic signal transduction relay by developing targeted therapeutic interventions aimed at angiogenesis suppression

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012997-02
Application #
6623853
Study Section
Pathology A Study Section (PTHA)
Program Officer
Dudley, Peter A
Project Start
2002-04-01
Project End
2007-02-28
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
2
Fiscal Year
2003
Total Cost
$319,679
Indirect Cost

  Institution

Name
Boston University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118

  Publications

Maghsoudlou, Armin; Meyer, Rosana D; Rezazadeh, Kobra et al. (2016) RNF121 Inhibits Angiogenic Growth Factor Signaling by Restricting Cell Surface Expression of VEGFR-2. Traffic 17:289-300
Rahimi, Nader; Golde, Todd E; Meyer, Rosana D (2009) Identification of ligand-induced proteolytic cleavage and ectodomain shedding of VEGFR-1/FLT1 in leukemic cancer cells. Cancer Res 69:2607-14
Singh, Amrik J; Meyer, Rosana D; Navruzbekov, Gyulmagomed et al. (2007) A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCgamma1 activation and angiogenesis. Proc Natl Acad Sci U S A 104:5413-8
Meyer, Rosana D; Qian, Xiaofeng; Guo, Hwai-Chen et al. (2006) Leucine motif-dependent tyrosine autophosphorylation of type III receptor tyrosine kinases. J Biol Chem 281:8620-7
Meyer, Rosana D; Mohammadi, Moosa; Rahimi, Nader (2006) A single amino acid substitution in the activation loop defines the decoy characteristic of VEGFR-1/FLT-1. J Biol Chem 281:867-75
Rahimi, Nader (2006) VEGFR-1 and VEGFR-2: two non-identical twins with a unique physiognomy. Front Biosci 11:818-29
Rahimi, Nader (2006) Vascular endothelial growth factor receptors: molecular mechanisms of activation and therapeutic potentials. Exp Eye Res 83:1005-16
Singh, Amrik J; Meyer, Rosana D; Band, Hamid et al. (2005) The carboxyl terminus of VEGFR-2 is required for PKC-mediated down-regulation. Mol Biol Cell 16:2106-18
Meyer, Rosana D; Singh, Amrik; Majnoun, Fredric et al. (2004) Substitution of C-terminus of VEGFR-2 with VEGFR-1 promotes VEGFR-1 activation and endothelial cell proliferation. Oncogene 23:5523-31
Meyer, Rosana D; Singh, Amrik J; Rahimi, Nader (2004) The carboxyl terminus controls ligand-dependent activation of VEGFR-2 and its signaling. J Biol Chem 279:735-42

Showing the most recent 10 out of 13 publications