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Artificially controlled aggregation of proteins and targeting in hematopoietic cells

Rosén, Hanna LU ; Gao, Ying LU ; Johnsson, E and Olsson, Inge LU (2003) In Journal of Leukocyte Biology 74(5). p.800-809
Abstract
The targeting mechanisms for granule proteins in hematopoietic cells are largely unknown. Aggregation is believed to be important for protein sorting-for-entry and sorting-by-retention in endocrine and neuroendocrine cells. We asked whether artificially induced multimerization/aggregation of chimeric proteins could affect their sorting in hematopoietic cells. A system was used that permits ligand-controlled intracellular oligomerization of hybrid proteins containing the FK506-binding protein (FKBP). The hybrid proteins ELA(FKBP)(3) with neutrophil elastase (ELA) and (FKBP*)(4)-FCS-hGH with a furin cleavage site (FCS) and human growth hormone (hGH) were expressed in the myeloblastic 32D and the rat basophilic leukemia (RBL-1) hematopoietic... (More)
The targeting mechanisms for granule proteins in hematopoietic cells are largely unknown. Aggregation is believed to be important for protein sorting-for-entry and sorting-by-retention in endocrine and neuroendocrine cells. We asked whether artificially induced multimerization/aggregation of chimeric proteins could affect their sorting in hematopoietic cells. A system was used that permits ligand-controlled intracellular oligomerization of hybrid proteins containing the FK506-binding protein (FKBP). The hybrid proteins ELA(FKBP)(3) with neutrophil elastase (ELA) and (FKBP*)(4)-FCS-hGH with a furin cleavage site (FCS) and human growth hormone (hGH) were expressed in the myeloblastic 32D and the rat basophilic leukemia (RBL-1) hematopoietic cell lines. ELA alone is normally targeted to secretory lysosomes. However, the hybrid proteins and ligand-induced aggregates of them were constitutively secreted and not targeted. The hGH that was released at the FCS in (FKBP*)(4)-FCS-hGH was also constitutively secreted. We conclude that protein multimerization/aggregation per se is not enough to facilitate sorting-for-entry to secretory lysosomes in hematopoietic cells and that improperly folded proteins may be eliminated from sorting by constitutive secretion. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
secretary lysosomes, storage, multimerization, quality control, secretion
in
Journal of Leukocyte Biology
volume
74
issue
5
pages
800 - 809
publisher
John Wiley & Sons Inc.
external identifiers
  • wos:000187392400021
  • pmid:12960262
  • scopus:0347991982
  • pmid:12960262
ISSN
1938-3673
DOI
10.1189/jlb.0203066
language
English
LU publication?
yes
id
7e29d3a5-06e9-4766-9d52-c066dbf871b5 (old id 292388)
date added to LUP
2016-04-01 11:57:09
date last changed
2022-01-26 20:38:27
@article{7e29d3a5-06e9-4766-9d52-c066dbf871b5,
  abstract     = {{The targeting mechanisms for granule proteins in hematopoietic cells are largely unknown. Aggregation is believed to be important for protein sorting-for-entry and sorting-by-retention in endocrine and neuroendocrine cells. We asked whether artificially induced multimerization/aggregation of chimeric proteins could affect their sorting in hematopoietic cells. A system was used that permits ligand-controlled intracellular oligomerization of hybrid proteins containing the FK506-binding protein (FKBP). The hybrid proteins ELA(FKBP)(3) with neutrophil elastase (ELA) and (FKBP*)(4)-FCS-hGH with a furin cleavage site (FCS) and human growth hormone (hGH) were expressed in the myeloblastic 32D and the rat basophilic leukemia (RBL-1) hematopoietic cell lines. ELA alone is normally targeted to secretory lysosomes. However, the hybrid proteins and ligand-induced aggregates of them were constitutively secreted and not targeted. The hGH that was released at the FCS in (FKBP*)(4)-FCS-hGH was also constitutively secreted. We conclude that protein multimerization/aggregation per se is not enough to facilitate sorting-for-entry to secretory lysosomes in hematopoietic cells and that improperly folded proteins may be eliminated from sorting by constitutive secretion.}},
  author       = {{Rosén, Hanna and Gao, Ying and Johnsson, E and Olsson, Inge}},
  issn         = {{1938-3673}},
  keywords     = {{secretary lysosomes; storage; multimerization; quality control; secretion}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{800--809}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Journal of Leukocyte Biology}},
  title        = {{Artificially controlled aggregation of proteins and targeting in hematopoietic cells}},
  url          = {{http://dx.doi.org/10.1189/jlb.0203066}},
  doi          = {{10.1189/jlb.0203066}},
  volume       = {{74}},
  year         = {{2003}},
}