Advanced

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)
Please use this url to cite or link to this publication:
author
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
Society for Leukocyte Biology
external identifiers
  • wos:000187392400021
  • pmid:12960262
  • scopus:0347991982
ISSN
1938-3673
DOI
language
English
LU publication?
yes
id
7e29d3a5-06e9-4766-9d52-c066dbf871b5 (old id 292388)
date added to LUP
2007-09-20 18:34:50
date last changed
2018-05-29 11:48:10
@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},
  keyword      = {secretary lysosomes,storage,multimerization,quality control,secretion},
  language     = {eng},
  number       = {5},
  pages        = {800--809},
  publisher    = {Society for Leukocyte Biology},
  series       = {Journal of Leukocyte Biology},
  title        = {Artificially controlled aggregation of proteins and targeting in hematopoietic cells},
  url          = {http://dx.doi.org/},
  volume       = {74},
  year         = {2003},
}