Identification of novel protein kinases in vascular cells

Protein kinases play pivotal roles in almost all signal transduction pathways in eukaryotic cells (1-4) and are implicated in most major human diseases, including atherosclerosis and associated vasculoproliferative disorders of arteries such as restenosis and graft stenosis (5). Several hundred distinct kinases have already been molecularly cloned, and it is likely that as a result of new information generated through large-scale genome sequencing projects this number will increase. Despite this flood of information, and with several important exceptions, there is a relative lack of knowledge regarding the identity of kinases specifically expressed in vascular tissues or cells and more particularly, it remains unclear how the expression of kinases alters in cardiovascular disease states. The first step in approaching this question is to identify the repertoire of kinases present in vascular tissues and cells. The protein tyrosine kinase (PTK) receptors for several polypeptide growth factors, including platelet-derived growth factor (PDGF), insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) have been implicated in neo-intimal and atherosclerotic disease (5). Apart from these and a few other exceptions, surprisingly little is known regarding the patterns of expression of specific PTKs or other kinases in neo-intima formation. The use of anti-phosphotyrosine antibodies, selective tyrosine kinase inhibitors and kinase-specific antibodies is limited.