Abstract
Lsc (the murine homolog of human p115 Rho GEF) is a member of the Dbl-homology family of GTP exchange factors and is a specific activator of Rho. Lsc is activated by the G alpha(13) subunit of heterotrimeric G proteins and contains a regulator of G protein signaling domain that downmodulates G alpha(12) and G alpha(13). Lsc is expressed primarily in the hematopoietic system and links the activation of G alpha(12) and G alpha(13)-coupled receptors to actin polymerization in B and T cells. Lsc is essential for marginal zone B (MZB) cell homeostasis and for the generation of immune responses. Although Lsc-deficient lymphocytes show reduced basal motility, MZB cells show enhanced migration after serum activation. Thus, Lsc is a critical regulator of MZB cells and immune functions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / immunology*
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Cells, Cultured
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Chemotaxis, Leukocyte*
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DNA-Binding Proteins / metabolism
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GTP-Binding Protein alpha Subunits, G12-G13
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Gene Targeting
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Guanine Nucleotide Exchange Factors*
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Hematopoietic Stem Cells / immunology
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Heterotrimeric GTP-Binding Proteins / metabolism
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Immunoglobulins / biosynthesis
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Lymphocyte Activation
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Lymphocyte Subsets / classification
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Lymphoid Tissue / immunology
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Mice
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Mice, Knockout
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Platelet Aggregation
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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Recombination, Genetic
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Rho Guanine Nucleotide Exchange Factors
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Tissue Distribution
Substances
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Arhgef1 protein, mouse
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DNA-Binding Proteins
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Guanine Nucleotide Exchange Factors
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Immunoglobulins
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Proto-Oncogene Proteins
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Rho Guanine Nucleotide Exchange Factors
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GTP-Binding Protein alpha Subunits, G12-G13
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Heterotrimeric GTP-Binding Proteins