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Nat Med. 2004 Sep;10(9):982-6. Epub 2004 Aug 29.

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

Author information

1
Department of Brain and Cognitive Sciences, and McGovern Institute for Brain Research, Massachusetts Institute of Technology, 45 Carleton Street, E25-618, Cambridge, Massachusetts 02139, USA.

Erratum in

  • Nat Med. 2004 Oct;10(10):1139.

Abstract

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.

PMID:
15334074
DOI:
10.1038/nm1098
[Indexed for MEDLINE]

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