Identification and characterization of a dimerization domain in CED-6, an adapter protein involved in engulfment of apoptotic cells
- Author
- Hua Poo Su, Enrico Brugnera, Wim Van Criekinge (UGent) , Elke Smits, Michael Hengartner, Thierry Bogaert and Kodimangalam S Ravichandran
- Organization
- Abstract
- Phagocytosis of apoptotic cells is a key step in the completion of programmed cell death that occurs throughout life in multicellular organisms. The molecular events involved in clearance of apoptotic cells are just beginning to be elucidated. Recently, CED-6, an adapter protein involved in engulfment has been cloned in Caenorhabditis elegans and in humans. CED-6 is composed of a phosphotyrosine-binding (PTB) domain and a proline-rich C-terminal domain with no apparent catalytic domain. Since PTB domains, originally identified in Shc, mediate intracellular signaling downstream of cell surface receptors, CED-6 has also been proposed to mediate intracellular signals leading to engulfment. In this report, we demonstrate that CED-6 dimerizes through a leucine zipper domain that is immediately adjacent to the PTB domain, Several lines of evidence based on co-immunoprecipitation studies, yeast two-hybrid assays, and gel filtration studies suggest that CED-B exists as a dimer in vivo. Through mutational analyses, we show that the leucine zipper is necessary and sufficient for CED-6 dimerization and that this dimerization is conserved among C. elegans, rodent, and human CED-6 proteins. We propose that dimerization may have unique implications for ligand binding via CED-6 and its function during the phagocytosis of apoptotic cells.
- Keywords
- PHAGOCYTOSIS, RECOGNITION, SHC, PHOSPHOTYROSINE-BINDING DOMAIN, IN-VIVO, RECEPTOR, ELEGANS, DEATH
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-791270
- MLA
- Su, Hua Poo, et al. “Identification and Characterization of a Dimerization Domain in CED-6, an Adapter Protein Involved in Engulfment of Apoptotic Cells.” JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 275, no. 13, 2000, pp. 9542–49, doi:10.1074/jbc.275.13.9542.
- APA
- Su, H. P., Brugnera, E., Van Criekinge, W., Smits, E., Hengartner, M., Bogaert, T., & Ravichandran, K. S. (2000). Identification and characterization of a dimerization domain in CED-6, an adapter protein involved in engulfment of apoptotic cells. JOURNAL OF BIOLOGICAL CHEMISTRY, 275(13), 9542–9549. https://doi.org/10.1074/jbc.275.13.9542
- Chicago author-date
- Su, Hua Poo, Enrico Brugnera, Wim Van Criekinge, Elke Smits, Michael Hengartner, Thierry Bogaert, and Kodimangalam S Ravichandran. 2000. “Identification and Characterization of a Dimerization Domain in CED-6, an Adapter Protein Involved in Engulfment of Apoptotic Cells.” JOURNAL OF BIOLOGICAL CHEMISTRY 275 (13): 9542–49. https://doi.org/10.1074/jbc.275.13.9542.
- Chicago author-date (all authors)
- Su, Hua Poo, Enrico Brugnera, Wim Van Criekinge, Elke Smits, Michael Hengartner, Thierry Bogaert, and Kodimangalam S Ravichandran. 2000. “Identification and Characterization of a Dimerization Domain in CED-6, an Adapter Protein Involved in Engulfment of Apoptotic Cells.” JOURNAL OF BIOLOGICAL CHEMISTRY 275 (13): 9542–9549. doi:10.1074/jbc.275.13.9542.
- Vancouver
- 1.Su HP, Brugnera E, Van Criekinge W, Smits E, Hengartner M, Bogaert T, et al. Identification and characterization of a dimerization domain in CED-6, an adapter protein involved in engulfment of apoptotic cells. JOURNAL OF BIOLOGICAL CHEMISTRY. 2000;275(13):9542–9.
- IEEE
- [1]H. P. Su et al., “Identification and characterization of a dimerization domain in CED-6, an adapter protein involved in engulfment of apoptotic cells,” JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 275, no. 13, pp. 9542–9549, 2000.
@article{791270,
abstract = {{Phagocytosis of apoptotic cells is a key step in the completion of programmed cell death that occurs throughout life in multicellular organisms. The molecular events involved in clearance of apoptotic cells are just beginning to be elucidated. Recently, CED-6, an adapter protein involved in engulfment has been cloned in Caenorhabditis elegans and in humans. CED-6 is composed of a phosphotyrosine-binding (PTB) domain and a proline-rich C-terminal domain with no apparent catalytic domain. Since PTB domains, originally identified in Shc, mediate intracellular signaling downstream of cell surface receptors, CED-6 has also been proposed to mediate intracellular signals leading to engulfment. In this report, we demonstrate that CED-6 dimerizes through a leucine zipper domain that is immediately adjacent to the PTB domain, Several lines of evidence based on co-immunoprecipitation studies, yeast two-hybrid assays, and gel filtration studies suggest that CED-B exists as a dimer in vivo. Through mutational analyses, we show that the leucine zipper is necessary and sufficient for CED-6 dimerization and that this dimerization is conserved among C. elegans, rodent, and human CED-6 proteins. We propose that dimerization may have unique implications for ligand binding via CED-6 and its function during the phagocytosis of apoptotic cells.}},
author = {{Su, Hua Poo and Brugnera, Enrico and Van Criekinge, Wim and Smits, Elke and Hengartner, Michael and Bogaert, Thierry and Ravichandran, Kodimangalam S}},
issn = {{0021-9258}},
journal = {{JOURNAL OF BIOLOGICAL CHEMISTRY}},
keywords = {{PHAGOCYTOSIS,RECOGNITION,SHC,PHOSPHOTYROSINE-BINDING DOMAIN,IN-VIVO,RECEPTOR,ELEGANS,DEATH}},
language = {{eng}},
number = {{13}},
pages = {{9542--9549}},
title = {{Identification and characterization of a dimerization domain in CED-6, an adapter protein involved in engulfment of apoptotic cells}},
url = {{http://doi.org/10.1074/jbc.275.13.9542}},
volume = {{275}},
year = {{2000}},
}
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