Abstract
RasGRP, a guanyl nucleotide-releasing protein for the small guanosine triphosphatase Ras, was characterized. Besides the catalytic domain, RasGRP has an atypical pair of "EF hands" that bind calcium and a diacylglycerol (DAG)-binding domain. RasGRP activated Ras and caused transformation in fibroblasts. A DAG analog caused sustained activation of Ras-Erk signaling and changes in cell morphology. Signaling was associated with partitioning of RasGRP protein into the membrane fraction. Sustained ligand-induced signaling and membrane partitioning were absent when the DAG-binding domain was deleted. RasGRP is expressed in the nervous system, where it may couple changes in DAG and possibly calcium concentrations to Ras activation.
| Original language | English |
|---|---|
| Pages (from-to) | 1082-1086 |
| Number of pages | 5 |
| Journal | Science |
| Volume | 280 |
| Issue number | 5366 |
| DOIs | |
| Publication status | Published - 15 May 1998 |
Keywords
- amino acid sequence
- animals
- brain
- calcium
- calcium-calmodulin-dependent protein kinases
- catalysis
- cell cycle proteins
- cell line
- cell membrane
- cell size
- cell transformation, neoplastic
- cloning, molecular
- DNA, complementary
- DNA-binding proteins
- diglycerides
- genes, ras
- guanine nucleotide exchange factors
- guanosine diphosphate
- guanosine triphosphate
- molecular sequence data
- neurons
- phosphoprotein phosphatases
- rats
- recombinant fusion proteins
- signal transduction
- ras proteins
- ras-GRF1