Abstract
Members of the Rho family of small guanosine triphosphatases (GTPases) regulate the organization of the actin cytoskeleton; Rho controls the assembly of actin stress fibers and focal adhesion complexes, Rac regulates actin filament accumulation at the plasma membrane to produce lamellipodia and membrane ruffles, and Cdc42 stimulates the formation of filopodia. When microinjected into quiescent fibroblasts, Rho, Rac, and Cdc42 stimulated cell cycle progression through G1 and subsequent DNA synthesis. Furthermore, microinjection of dominant negative forms of Rac and Cdc42 or of the Rho inhibitor C3 transferase blocked serum-induced DNA synthesis. Unlike Ras, none of the Rho GTPases activated the mitogen-activated protein kinase (MAPK) cascade that contains the protein kinases c-Raf1, MEK (MAPK or ERK kinase), and ERK (extracellular signal-regulated kinase). Instead, Rac and Cdc42, but not Rho, stimulated a distinct MAP kinase, the c-Jun kinase JNK/SAPK (Jun NH2-terminal kinase or stress-activated protein kinase). Rho, Rac, and Cdc42 control signal transduction pathways that are essential for cell growth.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Amino Acid Sequence
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Animals
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Base Sequence
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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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DNA / biosynthesis
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G1 Phase*
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GTP Phosphohydrolases / metabolism*
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GTP-Binding Proteins / metabolism*
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 1
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Mice
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Microinjections
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Mitogen-Activated Protein Kinase Kinases*
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Mitogen-Activated Protein Kinases*
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Molecular Sequence Data
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Protein Serine-Threonine Kinases / metabolism
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-raf
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Signal Transduction*
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Transfection
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cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
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rac GTP-Binding Proteins
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rhoA GTP-Binding Protein
Substances
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Cell Cycle Proteins
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Proto-Oncogene Proteins
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DNA
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-raf
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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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MAP Kinase Kinase 1
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Map2k1 protein, mouse
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Mitogen-Activated Protein Kinase Kinases
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GTP Phosphohydrolases
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GTP-Binding Proteins
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cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
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rac GTP-Binding Proteins
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rhoA GTP-Binding Protein