Integrins that bind to vitronectin are highly expressed in neovasculature and play an important regulatory role in angiogenesis. At least two cytokine-induced pathways lead to angiogenesis in vivo, and evidence indicates that these pathways can be distinguished by their dependency on specific av integrins. Our objective is to define the molecules involved in alpha v beta3- alpha v beta5-selective angiogenic signaling. We hypothesize that (i) different molecules associate with each of these integrins after angiogenesis is triggered by a defined cytokine and (ii) the assembly of specific molecules associating with the beta3 or the beta5 cytoplasmic domain results in selective signaling. Two independent, yet complementary strategies will be used to approach these questions: isolation of antibodies against specific elements present in alpha v beta3 and alpha v beta5 focal adhesion preparations and panning of phage display peptide libraries on beta3 and beta 5 cytoplasmic domains. These studies will shed light into the molecular basis of selective signal transduction pathways initiated by alpha v beta3 and alpha v beta5. A better understanding of angiogenesis and new ways of manipulating such process in physiological and pathological situations may result from this work.
| Cardo-Vila, Marina; Arap, Wadih; Pasqualini, Renata (2003) Alpha v beta 5 integrin-dependent programmed cell death triggered by a peptide mimic of annexin V. Mol Cell 11:1151-62 |
