title: RanBPM is a phosphoprotein that associates with the plasma membrane and interacts with the integrin LFA-1.
abstract: Integrin adhesion receptors can act as signaling receptors that transmit information from the extracellular environment to the interior of the cell, affecting many fundamental cellular processes, such as cell motility, proliferation, differentiation, and survival. Integrin signaling depends on the formation of organized sub-membrane complexes that comprise cytoskeletal, adapter, and signaling molecules. The identification of molecules that interact with the cytoplasmic domain of integrins has been the focus of research aimed to elucidating the mechanistic basis of integrin signal transduction. We have identified RanBPM as a novel interactor of the beta(2) integrin LFA-1 in a yeast-two-hybrid screen. In the same assay, RanBPM also interacted with the beta(1) integrin cytoplasmic domain. We demonstrate that RanBPM is a peripheral membrane protein and that integrins and RanBPM interact in vitro and in vivo and co-localize at the cell membrane. We find that RanBPM is phosphorylated on serine residues; phosphorylation of RanBPM is increased by stress stimuli and decreased by treatment with the p38 kinase inhibitor SB203580. Transfection of RanBPM synergizes with LFA-1-mediated adhesion in the transcriptional activation of an AP-1-dependent promoter, indicating that the two proteins interact functionally as well. We suggest that RanBPM may constitute a molecular scaffold that contributes to coupling LFA-1 and other integrins with intracellular signaling pathways.
authors.affiliation: Laboratory of Immunoregulation, Department of Immunology, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris, France.
authors.forename: Simona
authors.initials: S
authors.lastname: Denti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Sirri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cheli
authors.forename: Lars
authors.initials: L
authors.lastname: Rogge
authors.forename: Giulio
authors.initials: G
authors.lastname: Innamorati
authors.forename: Stella
authors.initials: S
authors.lastname: Putignano
authors.forename: Monica
authors.initials: M
authors.lastname: Fabbri
authors.forename: Ruggero
authors.initials: R
authors.lastname: Pardi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bianchi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D019556:COS Cells; D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002470:Cell Survival; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D017930:Genes, Reporter; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019169:Jurkat Cells; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011725:Pyridines / Q000494:pharmacology; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction; D013347:Subcellular Fractions; D013601:T-Lymphocytes / Q000378:metabolism; D014018:Tissue Distribution; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques; D020931:ran GTP-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018821:CD18 Antigens; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D007093:Imidazoles; D016169:Lymphocyte Function-Associated Antigen-1; D009687:Nuclear Proteins; D011725:Pyridines; C116005:Ran binding protein 9; D012694:Serine; D020931:ran GTP-Binding Protein; C093642:SB 203580