The negative regulation of platelet function: extending the role of the ITIM

The central role of immune-receptorlike signaling mechanisms in the activation of platelets at sites of vascular injury is well established. Of equal importance to the regulatory systems that control the activation of platelets are those systems that negatively regulate platelets and thereby prevent inappropriate platelet activation and thrombosis. Recent reports have identified a new mechanism through which this may be achieved, which involves signaling via a receptor that contains an immunoreceptor tyrosine-based inhibitory motif (ITIM). The role of ITIMs in the control of platelet function is the subject of this review.