Abstract
Ras and Rac are membrane-associated GTPases that function as molecular switches activating intracellular mitogen-activated protein kinase (MAPK) cascades and other effector pathways in response to extracellular signals [1]. Activation of Ras and Rac into their GTP-bound conformations is directly controlled by specific guanine-nucleotide exchange factors (GEFs), which catalyze GDP release. Several Ras-specific GEFs that are related to the budding yeast protein Cdc25p have been described, whereas GEFs for Rac-related GTPases contain a region that is homologous to the oncoprotein DbI [2-3]. The Ras-GRF1 and Ras-GRF2 proteins, which couple Ras activation to serpentine receptors and calcium signals, contain both Cdc25 and DbI homology (DH) regions [3-4]. Here, we demonstrate that Ras-GRF2 is a bifunctional signaling protein that is able to bind and activate Ras and Rac, and thereby coordinate the activation of the extracellular-signal-regulated kinase (ERK) and stress-activated protein kinase (SAPK) pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anisomycin / pharmacology
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Cycle Proteins / metabolism
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Cell Line
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Enzyme Activation
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GTP Phosphohydrolases / metabolism*
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GTP-Binding Proteins / metabolism*
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Guanine Nucleotide Exchange Factors
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Humans
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Ionomycin / pharmacology
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases*
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Phosphoprotein Phosphatases / metabolism
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Proteins / metabolism*
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Recombinant Fusion Proteins / metabolism
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Recombinant Proteins / metabolism
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Signal Transduction
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Transfection
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rac GTP-Binding Proteins
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ras Guanine Nucleotide Exchange Factors
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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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Guanine Nucleotide Exchange Factors
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Proteins
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Recombinant Fusion Proteins
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Recombinant Proteins
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ras Guanine Nucleotide Exchange Factors
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ras-GRF1
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Ionomycin
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Anisomycin
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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Phosphoprotein Phosphatases
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GTP Phosphohydrolases
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GTP-Binding Proteins
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rac GTP-Binding Proteins
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ras Proteins