Opposing roles of integrin alpha6Abeta1 and dystroglycan in laminin-mediated extracellular signal-regulated kinase activation.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/115992
- author
- 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
- organization
- publishing date
- 2003
- 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
- 2016-04-01 12:33:33
- date last changed
- 2022-01-27 06:44:06
@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}},
doi = {{10.1091/mbc.E03-01-0852}},
volume = {{14}},
year = {{2003}},
}