Networks in signal transduction: the role of adaptor proteins in platelet activation

In multicellular organisms, the translation of externally applied signals i nto appropriate cellular responses is mediated by a multitude of complex in tracellular signalling cascades. The accurate function of these signalling pathways is based on the sound interaction of proteins of different categor ies such as transmembrane receptors, protein kinases, protein phosphatases and g-proteins in three-dimensional signalling complexes. During the past 1 0 years it has became evident that a new class of proteins termed adaptor p roteins is indispensable for the assembly of these intracellular signalling scaffolds. The primary function of adaptor proteins is to mediate protein- protein and protein-lipid interactions and thus to integrate receptor-media ted signals at the intracellular level and to couple signalling receptors t o cytosolic signalling pathways. In order to perform this task, adapter pro teins are equipped with particular protein-protein and/or protein-lipid int eraction modules allowing them to communicate with other signalling protein s. While the essential function of adaptor proteins is clearly established in a variety of cell types (e.g. immune cells), the current knowledge about their role in platelet activation is still in the beginning. Numerous adap tor proteins have been shown to be expressed in platelets and many of them seem to be involved in the assembly of signalling complexes after engagemen t of platelet receptors such as the collagen receptor glycoprotein VI (GPVI ), thrombin receptors, integrin receptors and the GP Ib receptor. This revi ew will focus on the functional role of the most extensively studied adapto r proteins during platelet activation.