期刊
NATURE MEDICINE
卷 10, 期 9, 页码 982-986出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm1098
关键词
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资金
- NHLBI NIH HHS [HL66105, P01 HL056949, P01-HL56949] Funding Source: Medline
- NICHD NIH HHS [R01 HD028341, R01-HD28341] Funding Source: Medline
- NIMH NIH HHS [F32-MH065815] Funding Source: Medline
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(1,2). 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 blood(1). 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.
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