2008 Russell Ross Memorial Lectureship in Vascular Biology—Activating and Inhibitory Receptors in Blood and Vascular Cells
The activation state of circulating blood cells is a tightly controlled process that is continuously influenced by both stimulatory and inhibitory events, and proper integration of the signals transduced by physical and chemical mediators to which cells are exposed is crucial for maintaining homeostasis. Studies carried out over the past 20 years has led to the identification of numerous plasma membrane receptors linked to intracellular signaling pathways that regulate cellular activation, signal transmission, and later, adaptation. Human platelets are both a valuable and clinically relevant model system in which to study such activating and inhibitory processes at the molecular level, as their dysregulation can lead to bleeding, inflammation, thrombosis, and cardiovascular disease. Platelets express G protein-coupled receptors, kinase- and phosphatase-linked receptors, and a host of adhesion molecules, and there is growing recognition that these are intricately intertwined, making rational intervention to control platelet activation and platelet aggregation an increasingly approachable, albeit challenging, possibility. This lecture will highlight our recent understanding of the complex interplay between immunoreceptor tyrosine-based activation motif (ITAM)–bearing and immunoreceptor tyrosine-based inhibitory motif (ITIM)–bearing receptors that exists in platelets and other vascular cells, with an emphasis on the role that such receptors play in human health and the treatment of cardiovascular disease.