Human CED-6 encodes a functional homologue of the Caenorhabditis elegans engulfment protein CED-6.
The rapid engulfment of apoptotic cells is a specialized innate immune response used by organisms to remove apoptotic cells. In mammals, several receptors that recognize apoptotic cells have been identified; molecules that transduce signals from these receptors to downstream cytoskeleton molecules have not been found, however [1] [2] [3]. Our previous analysis of the engulfment gene ced-6 in Caenorhabditis elegans has suggested that CED-6 is an adaptor protein that participates in a signal transduction pathway that mediates the specific recognition and engulfment of apoptotic cells [1]. Here, we describe our isolation and characterization of a human cDNA encoding a protein, hCED-6, with strong sequence similarity to C. elegans CED-6. As is the case with the worm protein, hCED-6 contains a phosphotyrosine-binding (PTB) domain and potential Src-homology domain 3 (SH3) binding sites. Both CED-6 and hCED-6 contain a predicted coiled-coil domain in the middle region. The hCED-6 protein lacks the extended carboxyl terminus found in worm CED-6; this carboxy-terminal extension appears not to be essential for CED-6 function in C. elegans, however. Overexpression of hCED-6 rescues the engulfment defect of ced-6 mutants in C. elegans significantly, suggesting that hCED-6 is a functional homologue of C. elegans CED-6. Human ced-6 is expressed widely in most human tissues. Thus, CED-6, and the CED-6 signal transduction pathway, might be conserved from C. elegans to humans and are present in most, if not all, human tissues.
Liu
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Cold Spring Harbor Laboratory, Laboratory of Immunology, National Institute of Allergy and Infectious Disease, National Institute of Health, Cold Spring Harbor, Bethesda, 11724, 20892, USA.
Hengartner
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D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary / Q000235:genetics; D020224:Expressed Sequence Tags; D005816:Genetic Complementation Test; D015801:Helminth Proteins / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D009928:Organ Specificity; D010750:Phosphoproteins / Q000235:genetics* / Q000502:physiology; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D051017:Apoptosis Regulatory Proteins; C112888:CED-6 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D015801:Helminth Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger