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

Raja, Srikumar M; Metkar, Sunil S; Honing, Stefan; Wang, Baikun; Russin, William A; Pipalia, Nina H; Menaa, Cheikh; Belting, Mattias LU ; Cao, Xuefang and Dressel, Ralf, et al. (2005) In Journal of Biological Chemistry 280(21). p.20752-20761
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... (More)
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. (Less)
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type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
280
issue
21
pages
20752 - 20761
publisher
ASBMB
external identifiers
  • pmid:15788411
  • scopus:20144380101
ISSN
1083-351X
DOI
10.1074/jbc.M501181200
language
English
LU publication?
no
id
88255dee-9b11-4621-b413-2949d88ce21b (old id 1132915)
date added to LUP
2008-06-23 14:24:23
date last changed
2017-05-28 03:37:03
@article{88255dee-9b11-4621-b413-2949d88ce21b,
  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.},
  author       = {Raja, Srikumar M and Metkar, Sunil S and Honing, Stefan and Wang, Baikun and Russin, William A and Pipalia, Nina H and Menaa, Cheikh and Belting, Mattias and Cao, Xuefang and Dressel, Ralf and Froelich, Christopher J},
  issn         = {1083-351X},
  language     = {eng},
  number       = {21},
  pages        = {20752--20761},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {A novel mechanism for protein delivery: granzyme B undergoes electrostatic exchange from serglycin to target cells},
  url          = {http://dx.doi.org/10.1074/jbc.M501181200},
  volume       = {280},
  year         = {2005},
}