Nature Medicine10, 982 - 986 (2004)
Published online: 29 August 2004; | doi:10.1038/nm1098
There is an Erratum (October 2004) associated with this Letter.
CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation
Jill R Crittenden1, 4, 5, Wolfgang Bergmeier2, 5, Yanyu Zhang1, Crystal L Piffath2, Yuqiong Liang3, Denisa D Wagner2, David E Housman4
& Ann M Graybiel1
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.
2
The CBR Institute for Biomedical Research and the Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
3
Department of Immunology, University of Washington, Box 357370, Seattle, Washington 98195, USA.
4
Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
5
These authors contributed equally to this work.
Correspondence should be addressed to Ann M Graybiel graybiel@mit.edu
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 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.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
