Filamin Binds to the Cytoplasmic Domain of the β1-Integrin

Abstract

Integrins play an important role in regulating cell adhesion, motility, and activation. In an effort to iden- tify intracellular proteins expressed by activated T cells that interact with the cytoplasmic domain of (CD29), we used the 1-integrin bait in the yeast two-hybrid system. Here we report that the cytoplasmic domain of 1-integrin cytoplasmic domain as 1-integrin specifically inter- acts with the cytoskeletal protein filamin. This interac- tion required all but the most carboxyl-terminal three residues of the cytoplasmic domain of 1, and the car- boxyl-terminal 477 residues of filamin containing the terminal 4.5 96-residue tandem repeats of filamin. To verify this interaction in vivo, we showed that filamin specifically coprecipitated with We also showed that recombinant filamin chimeric pro- teins were able to bind to the vitro. We observed that a subset of single point muta- tions in the cytoplasmic domain of 1 in mammalian cells. 1 cytoplasmic domain in 1, which had been previously reported to impair its function, disrupt the interaction between these findings suggest that the interaction between 1 and filamin. Taken together, 1 and filamin, which in turn can bind actin, provides a mechanism for the interaction of this cell surface recep- tor with cytoskeletal proteins and that this interaction plays a role in normal receptor function.