The cAMP-Epac-Rap1 pathway regulates cell spreading and cell adhesion to laminin-5 through, the α3β1 integrin but not the α6β4 integrin

Abstract

Laminin-5 is an important constituent of the basal lamina. The receptors for laminin-5, the integrins α3β1 and α6β4, 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 α3β1 and α6β4 mediate adhesion to laminin-5, only α3β1-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.