Rack1, a receptor for activated protein kinase C, interacts with integrin beta 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 2 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.
Liliental
J
J
Department of Medicine, Microbiology and Immunology, University of California at Los Angeles School of Medicine 90095, USA.
Chang
D D
DD
D000595:Amino Acid Sequence; D001665:Binding Sites; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018821:CD18 Antigens; D010455:Peptides; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C070301:peptide I; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate