Laminin isoforms differentially regulate adhesion, spreading, proliferation, and ERK activation of beta1 integrin-null cells.
The presence of many laminin receptors of the beta1 integrin family on most cells makes it difficult to define the biological functions of other major laminin receptors such as integrin alpha6beta4 and dystroglycan. We therefore tested the binding of a beta1 integrin-null cell line GD25 to four different laminin variants. The cells were shown to produce dystroglycan, which based on affinity chromatography bound to laminin-1, -2/4, and -10/11, but not to laminin-5. The cells also expressed the integrin alpha6Abeta4A variant. GD25 beta1 integrin-null cells are known to bind poorly to laminin-1, but we demonstrate here that these cells bind avidly to laminin-2/4, -5, and -10/11. The initial binding at 20 min to each of these laminins could be inhibited by an integrin alpha6 antibody, but not by a dystroglycan antibody. Hence, integrin alpha6Abeta4A of GD25 cells was identified as a major receptor for initial GD25 cell adhesion to three out of four tested laminin isoforms. Remarkably, cell adhesion to laminin-5 failed to promote cell spreading, proliferation, and extracellular signal-regulated kinase (ERK) activation, whereas all these responses occurred in response to adhesion to laminin-2/4 or -10/11. The data establish GD25 cells as useful tools to define the role integrin alpha6Abeta4A and suggest that laminin isoforms have distinctly different capacities to promote cell adhesion and signaling via integrin alpha6Abeta4A.
Kikkawa
Yamato
Y
Section for Cell and Developmental Biology, Department of Cell and Molecular Biology, Lund University, SE-22184 Lund, Sweden.
Yu
Hao
H
Genersch
Elke
E
Sanzen
Noriko
N
Sekiguchi
Kiyotoshi
K
Fässler
Reinhard
R
Campbell
Kevin P
KP
Talts
Jan F
JF
Ekblom
Peter
P
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D049030:Dystroglycans / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism*; D039161:Integrin alpha6beta4 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics*; D007797:Laminin / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D020033:Protein Isoforms / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D049030:Dystroglycans; D048049:Extracellular Signal-Regulated MAP Kinases; D039161:Integrin alpha6beta4; D019012:Integrin beta1; D007797:Laminin; D020033:Protein Isoforms; D000097794:Kalinin; C119013:laminin 10; C102645:laminin alpha 2