RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs

J O Ebinu, D A Bottorff, E Y Chan, S L Stang, R J Dunn, J C Stone

Research output: Contribution to journalArticle

506 Citations (Scopus)

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.

LanguageEnglish
Pages1082-1086
Number of pages5
JournalScience
Volume280
Issue number5366
DOIs
Publication statusPublished - 15 May 1998

Fingerprint

Diglycerides
Nucleotides
Calcium
Proteins
EF Hand Motifs
Guanosine
Nervous System
Catalytic Domain
Membrane Proteins
Fibroblasts
Ligands
Membranes

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

Ebinu, J. O., Bottorff, D. A., Chan, E. Y., Stang, S. L., Dunn, R. J., & Stone, J. C. (1998). RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs. Science, 280(5366), 1082-1086. https://doi.org/10.1126/science.280.5366.1082
Ebinu, J O ; Bottorff, D A ; Chan, E Y ; Stang, S L ; Dunn, R J ; Stone, J C. / RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs. In: Science. 1998 ; Vol. 280, No. 5366. pp. 1082-1086.
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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.",
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Ebinu, JO, Bottorff, DA, Chan, EY, Stang, SL, Dunn, RJ & Stone, JC 1998, 'RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs' Science, vol. 280, no. 5366, pp. 1082-1086. https://doi.org/10.1126/science.280.5366.1082

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 journalArticle

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

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DO - 10.1126/science.280.5366.1082

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SP - 1082

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