Isolation of Signaling Molecules Involved in Anigiogenic Pathways Mediated Alpha V Integrins
Abstract
Integrins that bind to vitronectin are highly expressed in neovasculature and play an important regulatory role in angiogenesis. There are at least two cytokine-dependent pathways that lead to angiogenesis in vivo, and there is evidence indicating that they can be distinguished by their dependency on specific alphav integrins. Here we aim to define what molecules are involved in alphavBeta3- and alphavbeta5- selective angiogenic signaling. We hypothesize that: (I) molecules that associate with either of those integrins after angiogenesis is triggered by defined cytokines are different; (ii) the assembly of specific molecules associating with the beta3 or beta5 cytoplasmic domains results in selective signaling. The strategy that will be used to approach these questions is based on the panning of phage peptide libraries of beta3 and beta5 cytoplasmic domains. We will also investigate whether phosphorylation events can modulate the interaction with such integrin cytoplasmic domain- binding peptides. Finally, by using microinjection-based techniques, we will study the effect of integrin cytoplasmic domain binding peptides in cell adhesion, migration and proliferation upon stimulation with factors that activate endothelial cells in vitro. These studies will shed light into molecular basis of selective signal transduction pathways initiated by alphavbeta3 and alphavbeta5. New ways of inhibiting angiogenesis, and ultimately, new strategies to treat breast cancer may result from this work.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA387699
Entities
People
- Marina Cardo-vila
Organizations
- Sanford Burnham Prebys Medical Discovery Institute