title: Calpain-mediated regulation of platelet signaling pathways.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
authors.forename: Shafi M
authors.initials: SM
authors.lastname: Kuchay
authors.forename: Athar H
authors.initials: AH
authors.lastname: Chishti
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D002154:Calpain / Q000502:physiology*; D051379:Mice; D015398:Signal Transduction
chemical_list: D002154:Calpain; C112682:Capn1 protein, mouse