In order to understand the biochemical basis for cellular responses involving specific genes, it is critical to obtain sufficient quantities of the purified protein products of the genes so that functional and structural studies can be performed. Each of the projects of this SCOR grant involves an attempt to understand a the cellular or animal level the importance of growth factors, receptors and downstream signaling proteins in either vascular development or atherosclerotic plaque formation. In order to fully understand in detail how these signaling cascades mediate cell growth, chemotaxis and adherence it is necessary to determine the functions of these proteins and how they make specific contacts with other cellular proteins. With this knowledge it will ultimately be possible to design drugs to specifically block or enhance signaling cascades involved in vascular development, atherosclerosis or restenosis. The first goal of this core is to express the various signaling proteins that are crucial to the other projects and to purify the proteins. The individual project leaders can then use these proteins for in vitro studies and for raising antibodies. In addition, a novel peptide library approach will be used to ascertain the optimal peptide sequence for binding to the various domains. This information will be used to design inhibitors and to predict in vivo targets of protein kinases and phosphatases involved in vascular signaling.
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