Vascular biologyCalpain-mediated regulation of platelet signaling pathwaysKuchay, Shafi M; Chishti, Athar HAuthor Information Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, USA Correspondence to Professor A.H. Chishti, Department of Pharmacology and Cancer Center, University of Illinois College of Medicine, 909 South Wolcott Avenue, Room 5097, Chicago, IL 60612, USA Tel: +1 312 355 1293; fax: +312 355 1297; e-mail: [email protected] Current Opinion in Hematology: May 2007 - Volume 14 - Issue 3 - p 249-254 doi: 10.1097/MOH.0b013e3280ef68f8 Buy Metrics Abstract Purpose of review There is considerable interest in understanding the function and mechanism of calpains in platelet aggregation, spreading, and granular secretion pathways. Recent insights from the calpain-1 knockout platelets suggest a pivotal role of these cysteine proteases in the regulation of outside-in signaling, aggregation, and clot retraction. Recent findings The calpain-1 knockout mouse provided direct evidence for the role of calpain-1 in platelet aggregation and clot retraction. Reduced tyrosine phosphorylation of platelet proteins correlated with reduced platelet aggregation and clot retraction. Future investigations of the mechanism of platelet defects in calpain-1 null mice may unveil the physiological functions of this important and elusive protease in mammalian cells. Summary This review focuses on the role of calpains in platelets with a particular emphasis on recent findings in calpain-1 null platelets. Previous studies used synthetic inhibitors to study the role of calpains in platelet function yielding useful information about the identification of calpain substrates. The development of calpain-1 null mice demonstrated that calpain-1 plays an important function in the regulation of platelet aggregation and clot retraction. Since the combined deletion of calpain-1 and calpain-2 genes results in embryonic lethality, the calpain-1 null mouse remains the only experimental model available to study the physiological role of calpains in mammalian cells. © 2007 Lippincott Williams & Wilkins, Inc.