title: Platelet signaling: a complex interplay between inhibitory and activatory networks.
abstract: The role of platelets in hemostasis and thrombosis is dependent on a complex balance of activatory and inhibitory signaling pathways. Inhibitory signals released from the healthy vasculature suppress platelet activation in the absence of platelet receptor agonists. Activatory signals present at a site of injury initiate platelet activation and thrombus formation; subsequently, endogenous negative signaling regulators dampen activatory signals to control thrombus growth. Understanding the complex interplay between activatory and inhibitory signaling networks is an emerging challenge in the study of platelet biology, and necessitates a systematic approach to utilize experimental data effectively. In this review, we will explore the key points of platelet regulation and signaling that maintain platelets in a resting state, mediate activation to elicit thrombus formation, or provide negative feedback. Platelet signaling will be described in terms of key signaling molecules that are common to the pathways activated by platelet agonists and can be described as regulatory nodes for both positive and negative regulators.
authors.affiliation: Institute of Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: Bye
authors.affiliation: Institute of Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Unsworth
authors.affiliation: Institute of Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Gibbins
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001081:Apyrase / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006487:Hemostasis; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008954:Models, Biological; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013927:Thrombosis / Q000503:physiopathology; D013928:Thromboxane A2 / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C407243:F11R protein, human; D016023:Integrins; D011956:Receptors, Cell Surface; D013928:Thromboxane A2; D017869:Cyclic GMP-Dependent Protein Kinases; D010738:Type C Phospholipases; D001081:Apyrase; C067869:CD39 antigen
keywords: blood platelets; hemostasis; platelet activation; review; thrombosis