The cAMP-Epac-Rap1 pathway regulates cell spreading and cell adhesion to laminin-5 through the alpha3beta1 integrin but not the alpha6beta4 integrin.
Laminin-5 is an important constituent of the basal lamina. The receptors for laminin-5, the integrins alpha3beta1 and alpha6beta4, have been associated with epithelial wound migration and carcinoma invasion. The signal transduction mechanisms that regulate these integrins are not well understood. We report here that the small GTPase Rap1 regulates the adhesion of a number of cell lines to various extracellular matrix proteins including laminin-5. cAMP also mediates cell adhesion and spreading on laminin-5, a process that is independent of protein kinase A but rather dependent on Epac1, a cAMP-dependent exchange factor for Rap. Interestingly, although both alpha3beta1 and alpha6beta4 mediate adhesion to laminin-5, only alpha3beta1-dependent adhesion is dependent on Rap1. These results provide evidence for a function of the cAMP-Epac-Rap1 pathway in cell adhesion and spreading on different extracellular matrix proteins. They also define different roles for the laminin-binding integrins in regulated cell adhesion and subsequent cell spreading.
Biotechnology Centre of Oslo, University of Oslo, Blindern, N-0317 Oslo, Norway.
Jorrit M
JM
Enserink
Leo S
LS
Price
Trond
T
Methi
Milada
M
Mahic
Arnoud
A
Sonnenberg
Johannes L
JL
Bos
Kjetil
K
Taskén
D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002469:Cell Separation; D000242:Cyclic AMP / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism*; D039161:Integrin alpha6beta4 / Q000378:metabolism*; D020014:K562 Cells; D007797:Laminin / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*; D000097794:Kalinin
D000199:Actins; D015815:Cell Adhesion Molecules; D000242:Cyclic AMP; D018076:DNA, Complementary; D049452:Green Fluorescent Proteins; D020662:Guanine Nucleotide Exchange Factors; D039201:Integrin alpha3beta1; D039161:Integrin alpha6beta4; D007797:Laminin; D020827:rap1 GTP-Binding Proteins; D000097794:Kalinin; C116122:RAPGEF3 protein, human