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Opposing roles of integrin alpha6Abeta1 and dystroglycan in laminin-mediated extracellular signal-regulated kinase activation.

Ferletta, Maria LU ; Kikkawa, Yamato; Yu, Hao LU ; Talts, Jan LU ; Durbeej, Madeleine; Sonnenberg, Arnoud; Timpl, Rupert; Campbell, Kevin P; Ekblom, Peter LU and Genersch, Elke (2003) In Molecular Biology of the Cell 14(5). p.2088-2103
Abstract
Laminin–integrin interactions can in some settings activate the extracellular signal-regulated kinases (ERKs) but the control mechanisms are poorly understood. Herein, we studied ERK activation in response to two laminins isoforms (-1 and -10/11) in two epithelial cell lines. Both cell lines expressed {beta}1-containing integrins and dystroglycan but lacked integrin {alpha}6{beta}4. Antibody perturbation assays showed that both cell lines bound to laminin-10/11 via the {alpha}3{beta}1and {alpha}6{beta}1 integrins. Although laminin-10/11 was a stronger adhesion complex than laminin-1 for both cell lines, both laminins activated ERK in only one of the two cell lines. The ERK activation was mediated by integrin {alpha}6{beta}1 and not by... (More)
Laminin–integrin interactions can in some settings activate the extracellular signal-regulated kinases (ERKs) but the control mechanisms are poorly understood. Herein, we studied ERK activation in response to two laminins isoforms (-1 and -10/11) in two epithelial cell lines. Both cell lines expressed {beta}1-containing integrins and dystroglycan but lacked integrin {alpha}6{beta}4. Antibody perturbation assays showed that both cell lines bound to laminin-10/11 via the {alpha}3{beta}1and {alpha}6{beta}1 integrins. Although laminin-10/11 was a stronger adhesion complex than laminin-1 for both cell lines, both laminins activated ERK in only one of the two cell lines. The ERK activation was mediated by integrin {alpha}6{beta}1 and not by {alpha}3{beta}1 or dystroglycan. Instead, we found that dystroglycan-binding domains of both laminin-1 and -10/11 suppressed integrin {alpha}6{beta}1-mediated ERK activation. Moreover, the responding cell line expressed the two integrin {alpha}6 splice variants, {alpha}6A and {alpha}6B, whereas the nonresponding cell line expressed only {alpha}6B. Furthermore, ERK activation was seen in cells transfected with the integrin {alpha}6A subunit, but not in {alpha}6B-transfected cells. We conclude that laminin-1 and -10/11 share the ability to induce ERK activation, that this is regulated by integrin {alpha}6A{beta}1, and suggest a novel role for dystroglycan-binding laminin domains as suppressors of this activation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Biology of the Cell
volume
14
issue
5
pages
2088 - 2103
publisher
American Society for Cell Biology
external identifiers
  • wos:000182907100029
  • pmid:12802077
  • scopus:12444289493
ISSN
1939-4586
DOI
10.1091/mbc.E03-01-0852
language
English
LU publication?
yes
id
f1fad1df-49b4-48ce-b314-2a5d6017ec59 (old id 115992)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12802077&dopt=Abstract
date added to LUP
2007-07-12 10:37:03
date last changed
2018-01-07 06:21:15
@article{f1fad1df-49b4-48ce-b314-2a5d6017ec59,
  abstract     = {Laminin–integrin interactions can in some settings activate the extracellular signal-regulated kinases (ERKs) but the control mechanisms are poorly understood. Herein, we studied ERK activation in response to two laminins isoforms (-1 and -10/11) in two epithelial cell lines. Both cell lines expressed {beta}1-containing integrins and dystroglycan but lacked integrin {alpha}6{beta}4. Antibody perturbation assays showed that both cell lines bound to laminin-10/11 via the {alpha}3{beta}1and {alpha}6{beta}1 integrins. Although laminin-10/11 was a stronger adhesion complex than laminin-1 for both cell lines, both laminins activated ERK in only one of the two cell lines. The ERK activation was mediated by integrin {alpha}6{beta}1 and not by {alpha}3{beta}1 or dystroglycan. Instead, we found that dystroglycan-binding domains of both laminin-1 and -10/11 suppressed integrin {alpha}6{beta}1-mediated ERK activation. Moreover, the responding cell line expressed the two integrin {alpha}6 splice variants, {alpha}6A and {alpha}6B, whereas the nonresponding cell line expressed only {alpha}6B. Furthermore, ERK activation was seen in cells transfected with the integrin {alpha}6A subunit, but not in {alpha}6B-transfected cells. We conclude that laminin-1 and -10/11 share the ability to induce ERK activation, that this is regulated by integrin {alpha}6A{beta}1, and suggest a novel role for dystroglycan-binding laminin domains as suppressors of this activation.},
  author       = {Ferletta, Maria and Kikkawa, Yamato and Yu, Hao and Talts, Jan and Durbeej, Madeleine and Sonnenberg, Arnoud and Timpl, Rupert and Campbell, Kevin P and Ekblom, Peter and Genersch, Elke},
  issn         = {1939-4586},
  language     = {eng},
  number       = {5},
  pages        = {2088--2103},
  publisher    = {American Society for Cell Biology},
  series       = {Molecular Biology of the Cell},
  title        = {Opposing roles of integrin alpha6Abeta1 and dystroglycan in laminin-mediated extracellular signal-regulated kinase activation.},
  url          = {http://dx.doi.org/10.1091/mbc.E03-01-0852},
  volume       = {14},
  year         = {2003},
}