Rap1b is required for normal platelet function and hemostasis in mice

J Clin Invest. 2005 Mar;115(3):680-7. doi: 10.1172/JCI22973.


Rap1b, an abundant small GTPase in platelets, becomes rapidly activated upon stimulation with agonists. Though it has been implicated to act downstream from G protein-coupled receptors (GPCRs) and upstream of integrin alpha IIbbeta3, the precise role of Rap1b in platelet function has been elusive. Here we report the generation of a murine rap1b knockout and show that Rap1b deficiency results in a bleeding defect due to defective platelet function. Aggregation of Rap1b-null platelets is reduced in response to stimulation with both GPCR-linked and GPCR-independent agonists. Underlying the defective Rap1b-null platelet function is decreased activation of integrin alphaIIbbeta3 in response to stimulation with agonists and signaling downstream from the integrin alpha IIbbeta3. In vivo, Rap1b-null mice are protected from arterial thrombosis. These data provide genetic evidence that Rap1b is involved in a common pathway of integrin activation, is required for normal hemostasis in vivo, and may be a clinically relevant antithrombotic therapy target.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Platelets / metabolism*
  • Bone Marrow Transplantation
  • Carotid Arteries / pathology
  • Carotid Arteries / physiology
  • Collagen / metabolism
  • Cyclic AMP / metabolism
  • Embryo, Mammalian / anatomy & histology
  • Embryo, Mammalian / physiology
  • Fibrinogen / metabolism
  • Hemostasis / physiology*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Platelet Aggregation / physiology
  • Purinergic Antagonists
  • Regional Blood Flow
  • rap GTP-Binding Proteins / genetics
  • rap GTP-Binding Proteins / metabolism*


  • Purinergic Antagonists
  • Fibrinogen
  • Collagen
  • Cyclic AMP
  • Rap1b protein, mouse
  • rap GTP-Binding Proteins