Interactions between vascular cells and matrix proteins are mediated by integrins. These reactions are essential for vascular homeostasis and play an important role in thrombosis and hemostasis. Key integrins in the vasculature include glycoproteins llb/llla (allbb3) on the platelet surface and the fibronectin receptor (FnR, a5b1) and vitronectine receptor (avb3 and avb5) on the surface of endothelial and other cells. Studies performed as part of the Program Project and in other laboratories have shown that the interaction between integrin receptors and their ligands not only define a mechanism for cell adhesion and aggregation, but also initiates a variety of cellular signals that are essential for diverse cellular functions such as motility, production of cytokines, and cell division. These signals include activation of kinases, rearrangement of the cellular cytoskeleton and induction of genes. The overall focus of this Program Project continues to be on the identification and characterization of pathways through which these integrin-mediated signals are transduced. The function of CIB, a calcium and integrin binding protein, in integrin activation will be determined. The role of the low molecular weight G protein, rap1b, in integrin activation will be examined using a knockout mouse. The role of VASP in actin polymerization and activation of integrins will be determined. The cooperative effects of integrin mediated cell anchorage and mitgoens on signal generation and regulation of cell cycle traverse will be explored. These studies should continue to clarify the roles of integrins as signal transduction molecules and the unique effects of these proteins in vascular biology.
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