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. 2005 May 27;280(21):20752-61.
doi: 10.1074/jbc.M501181200. Epub 2005 Mar 23.

A novel mechanism for protein delivery: granzyme B undergoes electrostatic exchange from serglycin to target cells

Srikumar M Raja  1 , Sunil S Metkar, Stefan Höning, Baikun Wang, William A Russin, Nina H Pipalia, Cheikh Menaa, Mattias Belting, Xuefang Cao, Ralf Dressel, Christopher J Froelich
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Free article

A novel mechanism for protein delivery: granzyme B undergoes electrostatic exchange from serglycin to target cells

Srikumar M Raja et al. J Biol Chem. .
Free article

Abstract

The molecular interaction of secreted granzyme B-serglycin complexes with target cells remains undefined. Targets exposed to double-labeled granzyme B-serglycin complexes show solely the uptake of granzyme B. An in vitro model demonstrates the exchange of the granzyme from serglycin to immobilized, sulfated glycosaminoglycans. Using a combination of cell binding and internalization assays, granzyme B was found to exchange to sulfated glycosaminoglycans and, depending on the cell type, to higher affinity sites. Apoptosis induced by purified granzyme B and cytotoxic T-cells was diminished in targets with reduced cell surface glycosaminoglycan content. A mechanism of delivery is proposed entailing electrostatic transfer of granzyme B from serglycin to cell surface proteins.

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