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.
| Language | English |
|---|---|
| Pages | 1082-1086 |
| Number of pages | 5 |
| Journal | Science |
| Volume | 280 |
| Issue number | 5366 |
| DOIs | |
| Publication status | Published - 15 May 1998 |
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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
Cite this
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RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs. / Ebinu, J O; Bottorff, D A; Chan, E Y; Stang, S L; Dunn, R J; Stone, J C.
In: Science, Vol. 280, No. 5366, 15.05.1998, p. 1082-1086.Research output: Contribution to journal › Article
TY - JOUR
T1 - RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs
AU - Ebinu, J O
AU - Bottorff, D A
AU - Chan, E Y
AU - Stang, S L
AU - Dunn, R J
AU - Stone, J C
PY - 1998/5/15
Y1 - 1998/5/15
N2 - 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.
AB - 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.
KW - amino acid sequence
KW - animals
KW - brain
KW - calcium
KW - calcium-calmodulin-dependent protein kinases
KW - catalysis
KW - cell cycle proteins
KW - cell line
KW - cell membrane
KW - cell size
KW - cell transformation, neoplastic
KW - cloning, molecular
KW - DNA, complementary
KW - DNA-binding proteins
KW - diglycerides
KW - genes, ras
KW - guanine nucleotide exchange factors
KW - guanosine diphosphate
KW - guanosine triphosphate
KW - molecular sequence data
KW - neurons
KW - phosphoprotein phosphatases
KW - rats
KW - recombinant fusion proteins
KW - signal transduction
KW - ras proteins
KW - ras-GRF1
U2 - 10.1126/science.280.5366.1082
DO - 10.1126/science.280.5366.1082
M3 - Article
VL - 280
SP - 1082
EP - 1086
JO - Science
T2 - Science
JF - Science
SN - 0036-8075
IS - 5366
ER -