| First Author | Crittenden JR | Year | 2004 |
| Journal | Nat Med | Volume | 10 |
| Issue | 9 | Pages | 982-6 |
| PubMed ID | 15334074 | Mgi Jnum | J:92864 |
| Mgi Id | MGI:3054646 | Doi | 10.1038/nm1098 |
| Citation | Crittenden JR, et al. (2004) CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation. Nat Med 10(9):982-986 |
| abstractText | 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. |
