RanBPM Is a Phosphoprotein That Associates with the Plasma Membrane and Interacts with the Integrin LFA-1

Simona Denti, Alessandra Sirri, Alessandra Cheli, Lars Rogge, Giulio Innamorati, Stella Putignano, Monica Fabbri, Ruggero Pardi, Elisabetta Bianchi

Research output: Contribution to journalArticlepeer-review

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 β2 integrin LFA-1 in a yeast-two-hybrid screen. In the same assay, RanBPM also interacted with the β1 integrin cytoplasmic domain. We demonstrate that Ran-BPM 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.

Original languageEnglish
Pages (from-to)13027-13034
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number13
DOIs
Publication statusPublished - Mar 26 2004

ASJC Scopus subject areas

  • Biochemistry

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