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Rap1b is required for normal platelet function and hemostasis in mice.

http://www.ncbi.nlm.nih.gov/pubmed/15696195

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.

Pubmed ID: 15696195 RIS Download

Mesh terms: Animals | Blood Platelets | Bone Marrow Transplantation | Carotid Arteries | Collagen | Cyclic AMP | Embryo, Mammalian | Fibrinogen | Hemostasis | Humans | Mice | Mice, Inbred C57BL | Mice, Knockout | Platelet Aggregation | Purinergic Antagonists | Regional Blood Flow | rap GTP-Binding Proteins

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Associated grants

  • Agency: NHLBI NIH HHS, Id: HL-45100
  • Agency: NHLBI NIH HHS, Id: P01 HL045100

Mouse Genome Informatics (Data, Gene Annotation)

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