Abstract
The C. elegans gene ced-12 functions in the engulfment of apoptotic cells and in cell migration, acting in a signaling pathway with ced-2 Crkll, ced-5 DOCK180, and ced-10 Rac GTPase and acting upstream of ced-10 Rac. ced-12 encodes a protein with a pleckstrin homology (PH) domain and an SH3 binding motif, both of which are important for ced-12 function. CED-12 acts in engulfing cells for cell corpse engulfment and interacts physically with CED-5, which contains an SH3 domain. CED-12 has Drosophila and human counterparts. Expression of CED-12 and its counterparts in murine Swiss 3T3 fibroblasts induced Rho GTPase-dependent formation of actin filament bundles. We propose that through interactions with membranes and with a CED-2/CED-5 protein complex, CED-12 regulates Rho/Rac GTPase signaling and leads to cytoskeletal reorganization by an evolutionarily conserved mechanism.
Publication types
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Research Support, Non-U.S. Gov't
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Comment
MeSH terms
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3T3 Cells
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Actins / metabolism
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Animals
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Apoptosis Regulatory Proteins
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Caenorhabditis elegans
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Caenorhabditis elegans Proteins*
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Carrier Proteins / chemistry
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism
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Cell Movement / physiology
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Cloning, Molecular
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Conserved Sequence
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Cytoskeletal Proteins*
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Cytoskeleton / metabolism*
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Drosophila
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Gene Expression / physiology
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Helminth Proteins / chemistry
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Helminth Proteins / genetics
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Helminth Proteins / metabolism
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Humans
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Molecular Sequence Data
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Mutation / physiology
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Phagocytosis / physiology
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Proline / genetics
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Protein Kinases / chemistry
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Protein Kinases / genetics
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Protein Kinases / metabolism
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-crk
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Proto-Oncogene Proteins*
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Sequence Homology, Amino Acid
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Signal Transduction / physiology*
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rac GTP-Binding Proteins / metabolism*
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rho GTP-Binding Proteins / metabolism*
Substances
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Actins
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Apoptosis Regulatory Proteins
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CED-10 protein, C elegans
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CED-12 protein, C elegans
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CED-5 protein, C elegans
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Caenorhabditis elegans Proteins
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Carrier Proteins
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Cytoskeletal Proteins
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Helminth Proteins
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Membrane Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-crk
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Proline
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Protein Kinases
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rac GTP-Binding Proteins
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rho GTP-Binding Proteins
Associated data
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GENBANK/AF416781
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GENBANK/AF417860
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GENBANK/AF417861