Abstract
RhoG, a member of the Rho family of GTPases, has been implicated as a regulator of the actin cytoskeleton. In this study, we show a novel function for the small GTPase RhoG on the regulation of the interferon-gamma promoter and nuclear factor of activated T cells (NFAT) gene transcription in lymphocytes. Optimal function of RhoG for the expression of these genes requires a calcium signal, normally provided by the antigen receptor. In addition, RhoG potentiation of NFAT requires the indirect activity of Rac and Cdc42; however, pathways distinct from those activated by Rac and Cdc42 mediate RhoG activation of NFAT-dependent transcription. Using effector domain mutants of RhoG we found that its ability to potentiate NFAT-dependent transcription correlates with its capacity to increase actin polymerization, supporting the suggestion that NFAT-dependent transcription is an actin-dependent process. RhoG also promotes T-cell spreading on fibronectin, a property that is independent of its ability to enhance NFAT-dependent transcription. Hence, these results implicate RhoG in leukocyte trafficking and the control of gene expression induced in response to antigen encounter.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism*
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Actins / ultrastructure
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B-Lymphocytes / physiology
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B-Lymphocytes / ultrastructure
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Calcium / metabolism
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Cell Cycle Proteins*
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Cells, Cultured
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Cytoskeleton / metabolism*
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Cytoskeleton / ultrastructure
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Fibronectins / metabolism
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GTP Phosphohydrolases / genetics
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GTP Phosphohydrolases / metabolism*
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Gene Expression Regulation
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Humans
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Interferon-gamma / genetics
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Jurkat Cells
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Leukocytes / cytology
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Leukocytes / metabolism
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Lymphocytes / cytology
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Lymphocytes / physiology*
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Lymphocytes / ultrastructure
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Mutation
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NFATC Transcription Factors
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Nuclear Proteins*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-vav
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Signal Transduction
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T-Lymphocytes / physiology
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T-Lymphocytes / ultrastructure
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription, Genetic
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cdc42 GTP-Binding Protein / genetics
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cdc42 GTP-Binding Protein / metabolism
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rac1 GTP-Binding Protein / genetics
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rac1 GTP-Binding Protein / metabolism
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rho GTP-Binding Proteins
Substances
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Actins
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Cell Cycle Proteins
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DNA-Binding Proteins
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Fibronectins
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NFATC Transcription Factors
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Nuclear Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-vav
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Transcription Factors
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VAV1 protein, human
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RHOG protein, human
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Interferon-gamma
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GTP Phosphohydrolases
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cdc42 GTP-Binding Protein
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rac1 GTP-Binding Protein
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rho GTP-Binding Proteins
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Calcium