RACK1, A RECEPTOR FOR ACTIVATED PROTEIN-KINASE-C, INTERACTS WITH INTEGRIN BETA-SUBUNIT

The integrin beta subunit cytoplasmic domains are important for activa tion-dependent cell adhesion and adhesion-dependent signaling events. We report an interaction between integrin beta subunit cytoplasmic dom ain and Rack1, a Trp-Asp (WD) repeat protein that has been shown to bi nd activated protein kinase C, The Rack1-binding site on integrin beta (2) subunit resides within a conserved, membrane proximal region. In t he yeast two-hybrid assay, WD repeats five to seven of Rack1 (Rack1-WD 5/7) 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 bet a(1) integrins in JY lymphoblastoid cells, Whereas Rack1-WD5/7 binds i ntegrins constitutively, the association of full length Rack1 to integ rins in vivo requires a treatment with phorbol esters, which promotes cell spreading and adhesion, These findings suggest that Rack1 may lin k protein kinase C directly to integrins and participate in the regula tion of integrin functions.