Integrins are heterodimeric adhesion receptors consisting of α- and β-subunits capable of binding extracellular matrix molecules as well as other adhesion receptors on neighbouring cells. These interactions induce various signal transduction pathways in many cell types, leading to cytoskeletal reorganization, phosphorylation and induction of gene expression. Integrin ligation leads to cytoplasmic protein–protein interactions requiring both integrin cytoplasmic domains, and these domains are initiation points for focal adhesion formation and subsequent signal transduction cascades. In previous studies we have shown that the very short cytoplasmic α1 tail is required for post-ligand events, such as cell spreading as well as actin stress-fibre formation. In the present paper we report that cells lacking the cytoplasmic domain of the α1 integrin subunit are unable to form proper focal adhesions and that phosphorylation on tyrosine residues of focal adhesion components is reduced on α1β1-specific substrates. The α1 cytoplasmic sequence is a specific recognition site for focal adhesion components like paxillin, talin, α-actinin and pp125FAK. It seems to account for α1-specific signalling, since when peptides that mimic the cytoplasmic domain of α1 are transferred into cells, they influence α1β1-specific adhesion, presumably by competing for binding partners. For α1 integrin/protein binding, the conserved Lys-Ile-Gly-Phe-Phe-Lys-Arg motif and, in particular, the two lysine residues, are important.
Displacement of the cytoplasmic domain recovers focal adhesion formation, cytoskeletal organization and motility in swapped integrin chimeras