Amplification loops - KU Leuven Kulak放大回路-鲁汶大学富农.docVIP

Amplification loops and signal transduction pathways in platelets Deckmyn H*., Vanhoorelbeke K., Ulrichts H., Schoolmeester A., Staelens S., De Meyer S. Laboratory for Thrombosis Research, IRC KU Leuven Campus Kortrijk, Kortrijk, Belgium *to whom correspondence should be addressed at Laboratory for Thrombosis Research, IRC KU Leuven Campus Kortrijk, E. Sabbelaan 53, B-8500 Kortrijk, Belgium Tel ++32 56 246422 fax ++32 56 246997 hans.deckmyn@kulak.ac.be Introduction Using commercial microarrays, it was demonstrated that the transcriptome of platelets is complex and estimated to contain some 6000 mRNA species(1). These represent proteins of diverse function, including receptors, ion channels, signaling molecules, kinases, phosphatases, structural, metabolic and regulatory proteins. Proteins involved in cellular communication and signal transduction are overrepresented and may make up half of the proteins present. This obviously points towards the importance of signal transduction in the functioning of platelets, and indeed the most prominent function of platelets is to react as quickly as possible towards activating signals and to proceed immediately towards a close platelet-platelet interaction to form a haemostatic plug. A simplified scheme of the events that take place is given in Fig.1: first platelets adhere to collagen, which causes initial activation signals resulting in a.o. increased levels of cytosolic Ca2+, that starts of a whole series of processes. One of these is the formation of thromboxane A2, that by interacting with its own receptor causes further increases in Ca2+. This finally activates integrin (IIb(3 to bind the symmetrical fibrinogen leading to platelet-platelet interaction or aggregation. As this whole process proceeds as a selfamplifying activation system, it is clear that it is equally important to control this activation machinery by signals, essentially coming from endothelial cells, to restrict the formation of a platelet p