Identification and characterization of a dimerization domain in CED-6, an adapter protein involved in engulfment of apoptotic cells

Su, H. P., Brugnera, E., Van Criekinge, W., Smits, E., Hengartner, M., Bogaert, T., Ravichandran, K. S. (March 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). pp. 9542-9549. ISSN 0021-9258

URL: http://www.ncbi.nlm.nih.gov/pubmed/10734103
DOI: 10.1074/jbc.275.13.9542

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.

Item Type: Paper
Uncontrolled Keywords: PHOSPHOTYROSINE-BINDING DOMAIN IN-VIVO SHC PHAGOCYTOSIS RECOGNITION RECEPTOR ELEGANS DEATH
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
CSHL Authors:
Communities: CSHL labs > Hengartner lab
Depositing User: Matt Covey
Date: March 2000
Date Deposited: 31 Jan 2014 14:56
Last Modified: 31 Jan 2014 14:56
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29401

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