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CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation.

Nature medicine | Sep 1, 2004

Signaling through the second messengers calcium and diacylglycerol (DAG) is a critical element in many biological systems. Integration of calcium and DAG signals has been suggested to occur primarily through protein kinase C family members, which bind both calcium and DAG. However, an alternative pathway may involve members of the CalDAG-GEF/RasGRP protein family, which have structural features (calcium-binding EF hands and DAG-binding C1 domains) that suggest they can function in calcium and DAG signal integration. To gain insight into the signaling systems that may be regulated by CalDAG-GEF/RasGRP family members, we have focused on CalDAG-GEFI, which is expressed preferentially in the brain and blood. Through genetic ablation in the mouse, we have found that CalDAG-GEFI is crucial for signal integration in platelets. Mouse platelets that lack CalDAG-GEFI are severely compromised in integrin-dependent aggregation as a consequence of their inability to signal through CalDAG-GEFI to its target, the small GTPase Rap1. These results suggest that analogous signaling defects are likely to occur in the central nervous system when CalDAG-GEFI is absent or compromised in function.

Pubmed ID: 15334074 RIS Download

Mesh terms: Animals | Blood Cell Count | Calcium | DNA Primers | DNA-Binding Proteins | Diglycerides | Flow Cytometry | Genotype | Guanine Nucleotide Exchange Factors | Immunohistochemistry | Mice | Mice, Knockout | Platelet Aggregation | Second Messenger Systems | Signal Transduction | Thrombosis | rap1 GTP-Binding Proteins

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Associated grants

  • Agency: NHLBI NIH HHS, Id: P01-HL56949
  • Agency: NIMH NIH HHS, Id: F32-MH065815
  • Agency: NHLBI NIH HHS, Id: HL66105
  • Agency: NICHD NIH HHS, Id: R01 HD028341
  • Agency: NHLBI NIH HHS, Id: P01 HL056949
  • Agency: NICHD NIH HHS, Id: R01-HD28341

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