Abstract
The adenomatous polyposis coli gene (APC) is mutated in familial adenomatous polyposis and in sporadic colorectal tumors. Here the APC gene product is shown to bind through its armadillo repeat domain to a Rac-specific guanine nucleotide exchange factor (GEF), termed Asef. Endogenous APC colocalized with Asef in mouse colon epithelial cells and neuronal cells. Furthermore, APC enhanced the GEF activity of Asef and stimulated Asef-mediated cell flattening, membrane ruffling, and lamellipodia formation in MDCK cells. These results suggest that the APC-Asef complex may regulate the actin cytoskeletal network, cell morphology and migration, and neuronal function.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenomatous Polyposis Coli Protein
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Amino Acid Sequence
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Animals
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Brain / metabolism
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Cell Line
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Cell Membrane / ultrastructure
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Cell Size
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Colon / cytology
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Colon / metabolism
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Cytoplasm / metabolism
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Cytoskeletal Proteins / metabolism*
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Guanine Nucleotide Exchange Factors / chemistry
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Guanine Nucleotide Exchange Factors / genetics
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Guanine Nucleotide Exchange Factors / metabolism*
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Guanosine Diphosphate / metabolism
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Humans
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Immunoblotting
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Intestinal Mucosa / cytology
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Intestinal Mucosa / metabolism
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Mice
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Molecular Sequence Data
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Neurons / metabolism
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Precipitin Tests
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Protein Binding
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Protein Structure, Tertiary
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Rats
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Recombinant Fusion Proteins / metabolism
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Rho Guanine Nucleotide Exchange Factors
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Signal Transduction
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Trans-Activators*
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Transfection
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Two-Hybrid System Techniques
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beta Catenin
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rac GTP-Binding Proteins / metabolism*
Substances
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ARHGEF4 protein, human
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Adenomatous Polyposis Coli Protein
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CTNNB1 protein, human
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CTNNB1 protein, mouse
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Ctnnb1 protein, rat
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Cytoskeletal Proteins
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Guanine Nucleotide Exchange Factors
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Recombinant Fusion Proteins
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Rho Guanine Nucleotide Exchange Factors
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Trans-Activators
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beta Catenin
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Guanosine Diphosphate
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rac GTP-Binding Proteins