alpha 1 Integrin cytoplasmic domain is involved in focal adhesion formation via association with intracellular proteins

Integrins are heterodimeric adhesion receptors consisting of alpha- and bet a -subunits capable of binding extracellular matrix molecules as well as ot her adhesion receptors on neighbouring cells. These interactions induce var ious signal transduction pathways in many cell types, leading to cytoskelet al reorganization, phosphorylation and induction of gene expression. Integr in ligation leads to cytoplasmic protein-protein interactions requiring bot h integrin cytoplasmic domains, and these domains are initiation points for focal adhesion formation and subsequent signal transduction cascades. In p revious studies we have shown that the very short cytoplasmic alpha1 tail i s 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 t he cytoplasmic domain of the alpha1 integrin subunit are unable to form pro per focal adhesions and that phosphorylation on tyrosine residues of focal adhesion components is reduced on alpha1 beta1-specific substrates. The alp ha1 cytoplasmic sequence is a specific recognition site for focal adhesion components like paxillin, talin, alpha -actinin and pp125FAK. It seems to a ccount for alpha1-specific signalling, since when peptides that mimic the c ytoplasmic domain of eel are transferred into cells, they influence alpha1 beta1-specific adhesion. presumably by competing for binding partners. For alpha1 integrin/ protein binding, the conserved Lys-Ile-Gly-Phe-Phe-Lys-Arg motif and, in particular, the two lysine residues, are important.