Rack1, a receptor for activated protein kinase C, interacts with integrin β subunit

The integrin beta subunit cytoplasmic domains are important for activation-dependent cell adhesion and adhesion-dependent signaling events. We report an interaction between integrin beta subunit cytoplasmic domain and Rack1, a Trp-Asp (WD) repeat protein that has been shown to bind activated protein kinase C, The Rack1-binding site on integrin beta(2) subunit resides within a conserved, membrane proximal region. In the yeast two-hybrid assay, WD repeats five to seven of Rack1 (Rack1-WD5/7) interact with integrin beta(1), beta(2), and beta(5) cytoplasmic domain, In eukaryotic cells, Rack1 co-immunoprecipitates with at least two different beta integrins, beta(1) integrins in 293T cells and beta(1) integrins in JY lymphoblastoid cells, Whereas Rack1-WD5/7 binds integrins constitutively, the association of full length Rack1 to integrins in vivo requires a treatment with phorbol esters, which promotes cell spreading and adhesion, These findings suggest that Rack1 may link protein kinase C directly to integrins and participate in the regulation of integrin functions.