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

Abstract

In multicellular organisms, the translation of externally applied signals into appropriate cellular responses is mediated by a multitude of complex intracellular signalling cascades. The accurate function of these signalling pathways is based on the sound interaction of proteins of different categories such as transmembrane receptors, protein kinases, protein phosphatases and g-proteins in three-dimensional signalling complexes. During the past 10 years it has became evident that a new class of proteins termed adaptor proteins 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-mediated signals at the intracellular level and to couple signalling receptors to cytosolic signalling pathways. In order to perform this task, adapter proteins are equipped with particular protein–protein and/or protein–lipid interaction modules allowing them to communicate with other signalling proteins. 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 adaptor proteins have been shown to be expressed in platelets and many of them seem to be involved in the assembly of signalling complexes after engagement of platelet receptors such as the collagen receptor glycoprotein VI (GPVI), thrombin receptors, integrin receptors and the GP Ib receptor. This review will focus on the functional role of the most extensively studied adaptor proteins during platelet activation.