Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1031
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.
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-6 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:||Journal Article, refereed|
|Communities & Collections:||07 Faculty of Science > Institute of Molecular Life Sciences|
|DDC:||570 Life sciences; biology|
|Date:||31 March 2000|
|Deposited On:||11 Feb 2008 12:20|
|Last Modified:||28 Nov 2013 00:36|
|Publisher:||American Society for Biochemistry and Molecular Biology|
|Citations:||Web of Science®. Times Cited: 35|
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