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- Title
CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation.
- Authors
Crittenden, Jill R.; Bergmeier, Wolfgang; Yanyu Zhang; Piffath, Crystal L.; Yuqiong Liang; Wagner, Denisa D.; Housman, David E.; Graybiel, Ann M.
- 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 integration1.2. 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 blood¹. 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 Rap 1. 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.
- Subjects
BIOCHEMISTRY; MEDICAL research; CALCIUM; DIGLYCERIDES; BIOLOGICAL systems; PROTEINS; MOLECULAR biology; PROTEIN kinase C; PROTEIN kinases; CENTRAL nervous system
- Publication
Nature Medicine, 2004, Vol 10, Issue 9, p982
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm1098