Abstract
The Son of Sevenless (Sos) proteins control receptor-mediated activation of Ras by catalyzing the exchange of guanosine diphosphate for guanosine triphosphate on Ras. The NH2-terminal region of Sos contains a Dbl homology (DH) domain in tandem with a pleckstrin homology (PH) domain. In COS-1 cells, the DH domain of Sos stimulated guanine nucleotide exchange on Rac but not Cdc42 in vitro and in vivo. The tandem DH-PH domain of Sos (DH-PH-Sos) was defective in Rac activation but regained Rac stimulating activity when it was coexpressed with activated Ras. Ras-mediated activation of DH-PH-Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3-kinase. These results reveal a potential mechanism for coupling of Ras and Rac signaling pathways.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / metabolism
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Animals
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COS Cells
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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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Cell Membrane / ultrastructure
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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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Guanosine Diphosphate / metabolism
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Guanosine Triphosphate / metabolism
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Humans
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JNK Mitogen-Activated Protein Kinases
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Membrane Proteins / chemistry
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Membrane Proteins / metabolism*
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Mitogen-Activated Protein Kinases*
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Proteins / metabolism
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins / metabolism
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Retroviridae Proteins, Oncogenic / chemistry
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Signal Transduction
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Son of Sevenless Proteins
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Transfection
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cdc42 GTP-Binding Protein
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rac GTP-Binding Proteins
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ras Guanine Nucleotide Exchange Factors
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ras Proteins / metabolism*
Substances
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Actins
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Cell Cycle Proteins
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Guanine Nucleotide Exchange Factors
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MCF2 protein, human
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Membrane Proteins
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Proteins
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins
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Retroviridae Proteins, Oncogenic
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Son of Sevenless Proteins
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ras Guanine Nucleotide Exchange Factors
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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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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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GTP Phosphohydrolases
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GTP-Binding Proteins
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cdc42 GTP-Binding Protein
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rac GTP-Binding Proteins
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ras Proteins