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Published on: January 30, 2009
Nerve growth factor activates persistent Rap1 signaling in endosomes
1Departments of Neurology and Neurological Sciences and of Pediatrics and the Program in Neuroscience, Stanford University School of Medicine, Stanford, California 94305, USA. cbwu@stanford.edu
Summary
Nerve growth factor (NGF) activates Rap1, a Ras family protein, and mitogen-activated protein kinase (MAPK) in endosomes. This sustained signaling is crucial for NGF
Area of Science:
- Cellular signaling
- Molecular biology
- Neuroscience
Background:
- Nerve growth factor (NGF) and epidermal growth factor (EGF) activate Ras, but their effects on Rap1 differ.
- Rap1 activation is sustained by NGF, correlating with mitogen-activated protein kinase (MAPK) pathway activation.
Purpose of the Study:
- Investigate the role of endogenous Rap1 in NGF signaling in PC12 cells.
- Elucidate the molecular mechanisms underlying NGF-induced Rap1 activation.
Main Methods:
- Utilized co-immunoprecipitation to identify protein complexes involved in Rap1 signaling.
- Employed confocal microscopy and subcellular fractionation to determine protein localization.
- Assessed the impact of brefeldin A (BFA) on NGF signaling pathways.
Main Results:
- NGF, but not EGF, induced sustained activation of Rap1.
- NGF triggered the formation of a stable C3G/CrkL/Shp2/Gab2/TrkA complex.
- Activated Rap1, TrkA, and MAPK were localized to endosomes.
- BFA treatment inhibited NGF-induced Rap1 and MAPK activation.
Conclusions:
- Endosomes serve as a platform for NGF-induced prolonged Rap1 and MAPK activation.
- The C3G/CrkL/Shp2/Gab2/TrkA complex is integral to Rap1 activation by NGF.
- Rap1 plays a critical role in sustained MAPK activation downstream of NGF.
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