Project: Research project

Project Details


DESCRIPTION: (Applicant's Description)

Anglogenesis (the formation of new blood capillaries) is an important
component of several normal physiological processes including development and
wound healing. Angiogenesis also contributes to the onset and spread of
disease, for example in cancer angiogenesis provides tumor cells with
essential nutrients and thus contributes to tumor growth. An
anti-angiogenesis strategy for fighting cancer is attractive because this
would target endothelial cells and potentially avoid the drug resistance
observed when targeting tumor cells. Vascular Endothelial Growth Factor
(VEGF) has received consideration as a target for angiogenesis inhibition for
several reasons: Its expression by tumor cells is augmented by a lack of
nutrients, VEGF's actions are specific to endothelial cells, and blocking
VEGF's actions will inhibit the growth of tumors grown in mice.

Information on the signal transduction pathways activated by VEGF is limited.
Previously, our laboratory discovered the KDR gene and identified it as a
receptor for VEGF. KDR is a receptor tyrosine kinase and we have identified
four autophosphorylation sites. The experiments proposed in this application
are directed at two goals. First, we wish to understand at a molecular level
how KDR autophosphorylation recruits cell signaling proteins. Second, we have
designed experiments to clarify the cellular consequence of specific
receptor/signaling protein interactions. Four Specific Aims are proposed to
accomplish these goals. Specific Aim 1 will determine whether there are
autophosphorylation sites in addition to the ones reported earlier. Specific
Aim 2 will test the hypothesis that receptor autophosphorylation in the kinase
domain is required for maximum catalytic activity. Specific Aim 3 is directed
at clarifying the signaling proteins which interact with receptor
autophosphorylation sites. Specific Aim 4 is directed at clarifying
endothelial cellular response which are dependent upon receptor
phosphorylation at specific tyrosines.
Effective start/end date8/16/994/30/10


  • National Cancer Institute: $301,024.00
  • National Cancer Institute: $301,024.00
  • National Cancer Institute: $310,015.00
  • National Cancer Institute: $301,024.00


  • Cell Biology
  • Medicine(all)
  • Oncology
  • Cancer Research


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