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beta 2 Integrins target Rap GTPases to the plasma membrane by means of degranulation

Dib, Karim LU ; Axelsson, Lena LU and Andersson, Tommy LU (2008) In Biochemical and Biophysical Research Communications 376(4). p.642-646
Abstract
We report the novel observation that engagement of beta 2 integrins on human neutrophils is accompanied by increased levels of the small GTPases Rap1 and Rap2 in a membrane-enriched fraction and a concomitant decrease of these proteins in a granule-enriched fraction. In parallel, we observed a similar time-dependent decrease of gelatinase B (a marker of specific and gelatinase B-containing granules) but not myeloperoxidase (a marker of azurophil granules) in the granule fraction, and release of lactoferrin (a marker of specific granules) in the extracellular medium. Furthermore, inhibition of Src tyrosine kinases, or phosphoinositide 3-kinase with PP1 or LY294002, respectively, blocked 02 integrin-induced degranulation and the... (More)
We report the novel observation that engagement of beta 2 integrins on human neutrophils is accompanied by increased levels of the small GTPases Rap1 and Rap2 in a membrane-enriched fraction and a concomitant decrease of these proteins in a granule-enriched fraction. In parallel, we observed a similar time-dependent decrease of gelatinase B (a marker of specific and gelatinase B-containing granules) but not myeloperoxidase (a marker of azurophil granules) in the granule fraction, and release of lactoferrin (a marker of specific granules) in the extracellular medium. Furthermore, inhibition of Src tyrosine kinases, or phosphoinositide 3-kinase with PP1 or LY294002, respectively, blocked 02 integrin-induced degranulation and the redistribution of Rap1 and Rap2 to a membrane-enriched fraction. Consequently, the 02 integrin-dependent exocytosis of specific and gelatinase B-containing granules occurs via a Src tyrosine kinase/phosphoinositide 3-kinase signaling pathway and is responsible for the translocation of Rap1 and Rap2 to the plasma membrane in human neutrophils. (C) 2008 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Signal transduction, beta 2 Integrins, Human neutrophils, Degranulation, Rap GTPases
in
Biochemical and Biophysical Research Communications
volume
376
issue
4
pages
642 - 646
publisher
Elsevier
external identifiers
  • wos:000260522300003
  • scopus:53449095256
ISSN
1090-2104
DOI
10.1016/j.bbrc.2008.08.160
language
English
LU publication?
yes
id
1971c88b-1c24-4a42-85eb-e7f1e114db70 (old id 1284810)
date added to LUP
2009-02-09 08:53:28
date last changed
2017-01-01 05:47:30
@article{1971c88b-1c24-4a42-85eb-e7f1e114db70,
  abstract     = {We report the novel observation that engagement of beta 2 integrins on human neutrophils is accompanied by increased levels of the small GTPases Rap1 and Rap2 in a membrane-enriched fraction and a concomitant decrease of these proteins in a granule-enriched fraction. In parallel, we observed a similar time-dependent decrease of gelatinase B (a marker of specific and gelatinase B-containing granules) but not myeloperoxidase (a marker of azurophil granules) in the granule fraction, and release of lactoferrin (a marker of specific granules) in the extracellular medium. Furthermore, inhibition of Src tyrosine kinases, or phosphoinositide 3-kinase with PP1 or LY294002, respectively, blocked 02 integrin-induced degranulation and the redistribution of Rap1 and Rap2 to a membrane-enriched fraction. Consequently, the 02 integrin-dependent exocytosis of specific and gelatinase B-containing granules occurs via a Src tyrosine kinase/phosphoinositide 3-kinase signaling pathway and is responsible for the translocation of Rap1 and Rap2 to the plasma membrane in human neutrophils. (C) 2008 Elsevier Inc. All rights reserved.},
  author       = {Dib, Karim and Axelsson, Lena and Andersson, Tommy},
  issn         = {1090-2104},
  keyword      = {Signal transduction,beta 2 Integrins,Human neutrophils,Degranulation,Rap GTPases},
  language     = {eng},
  number       = {4},
  pages        = {642--646},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {beta 2 Integrins target Rap GTPases to the plasma membrane by means of degranulation},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2008.08.160},
  volume       = {376},
  year         = {2008},
}