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Characterization of the biochemical and biophysical properties of the phosphatidylserine receptor (PS-R) gene product

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Abstract

The PS-R gene product was originally described as a cell surface receptor that interacts with externalized phosphatidylserine (PS) on apoptotic cells, but more recent studies have shown that it plays a critical role in organ development and terminal differentiation of many cell types during embryogenesis. Despite these important developmental functions, the biochemical and molecular properties of PS-R are poorly understood. Here we have used several approaches to show that PS-R undergoes processive post-translational protein cross-linking to form covalent multimers within the nuclear compartment. Although PS-R has a potential Glu-Glu (QQ) duet that is often targeted by transglutaminase TG-2, the oligomerization of PS-R was not effected by QQ→AA mutation, or when PS-R gene product was expressed in TG-2 (-/-) fibroblasts. Pulse-chase experiments with 35 S-methionine indicates that the PS-R undergoes an initial proteolytic cleavage, followed by progressive multimerization of the monomeric subunits over time. In summary, we report here that PS-R is modified by an unusual post-translational modification, and we speculate that homomultimer of PS-R might be playing an important function as a scaffolding protein in the nucleus.

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Acknowledgments

We would like Dr. Jens Bose (German Research Center for Biotechnology) for discussing unpublished data. We would also like to thank Dr. Valerie Fadok and Dr. Peter Henson (National Jewish Hospital, Denver, CO) for PS-R DNA, Dr. Gerry Melino, (University of Roma) for the TG-2 (-/-) cells, Dr. Richard Flavell (Yale University) for PS-R (-/-) cells and Veera D’mello. Dr. Charles Reichman and Dr. Carolyn Suzuki for critical comments on the manuscipt. This work was supported by a grant from the Arthritis Foundation and from the UMDNJ Research Foundation to R.B. Birge and NIH NS 046593 to H. Li.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ, 07103, USA

    Nitu Tibrewal & Raymond B. Birge

  2. Center for Advanced Proteomics Research and Department of Biochemistry and MolecularBiology, UMDNJ-New Jersey Medical School Cancer Center, Newark, NJ, 07103, USA

    Tong Liu & Hong Li

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  1. Nitu Tibrewal
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  2. Tong Liu
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  3. Hong Li
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  4. Raymond B. Birge
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Correspondence to Raymond B. Birge.

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Tibrewal, N., Liu, T., Li, H. et al. Characterization of the biochemical and biophysical properties of the phosphatidylserine receptor (PS-R) gene product. Mol Cell Biochem 304, 119–125 (2007). https://doi.org/10.1007/s11010-007-9492-8

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  • DOI: https://doi.org/10.1007/s11010-007-9492-8

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