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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Brain / metabolism*
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Calcium / metabolism
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Catalysis
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cell Line
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Cell Membrane / metabolism
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Cell Size
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Cell Transformation, Neoplastic
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Cloning, Molecular
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DNA, Complementary
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Diglycerides / metabolism
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Genes, ras
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Guanine Nucleotide Exchange Factors*
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Guanosine Diphosphate / metabolism
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Guanosine Triphosphate / metabolism
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Molecular Sequence Data
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Neurons / metabolism
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Phosphoprotein Phosphatases / genetics
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Phosphoprotein Phosphatases / metabolism
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Rats
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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ras Proteins / metabolism*
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ras-GRF1
Substances
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Cell Cycle Proteins
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DNA, Complementary
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DNA-Binding Proteins
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Diglycerides
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Guanine Nucleotide Exchange Factors
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Rasgrp1 protein, rat
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Recombinant Fusion Proteins
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ras-GRF1
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Guanosine Diphosphate
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Guanosine Triphosphate
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Calcium-Calmodulin-Dependent Protein Kinases
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Phosphoprotein Phosphatases
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ras Proteins
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Calcium