Protein-tyrosine phosphatases: a new frontier in platelet signal transduction

Platelet activation must be tightly controlled in order to allow platelets to respond rapidly to vascular injury and prevent thrombosis from occurring. Protein-tyrosine phosphorylation is one of the main ways in which activation signals are transmitted in platelets. Although much is known about the protein-tyrosine kinases (PTKs) that initiate and propagate activation signals, relatively little is known about the protein-tyrosine phosphatases (PTPs) that modulate these signals in platelets. PTPs are a family of enzymes that dephosphorylate tyrosine residues in proteins and regulate signals transmitted within cells. PTPs have been implicated in a variety of pathological conditions, including cancer, diabetes and autoimmunity, but their functions in hemostasis and thrombosis remain largely undefined. Exciting new findings from a number of groups have revealed that PTPs are in fact critical regulators of platelet activation and thrombosis. The primary aim of this review is to highlight the unique and important functions of PTPs in regulating platelet activity. Establishing the functions of PTPs in platelets is essential to better understand the molecular basis of thrombosis and may lead to the development of improved antithrombotic therapies.