Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity

Citation
E. Bianchi et al., Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity, NATURE, 404(6778), 2000, pp. 617
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary,Multidisciplinary,Multidisciplinary
Journal title
NATURE
ISSN journal
0028-0836 → ACNP
Volume
404
Issue
6778
Year of publication
2000
Database
ISI
SICI code
0028-0836(20000406)404:6778<617:ILIWTT>2.0.ZU;2-L
Abstract
Integrin adhesion receptors transduce signals that control complex cell fun ctions which require the regulation of gene expression, such as proliferati on, differentiation and survival(1). Their intracellular domain has no cata lytic function, indicating that interaction with other transducing molecule s is crucial for integrin-mediated signalling. Here we have identified a pr otein that interacts with the cytoplasmic domain of the beta 2 subunit of t he alpha L/beta 2 integrin LFA-1. This protein is JAB1 (Jun activation doma in-binding protein 1), a coactivator of the c-Jun transcription factor(2). We found that JAB1 is present both in the nucleus and in the cytoplasm of c ells and that a fraction of JAB1 colocalizes with LFA-1 at the cell membran e. LFA-1 engagement is followed by an increase of the nuclear pool of JAB1, paralleled by enhanced binding of c-Jun-containing AP-1 complexes to their DNA consensus site and increased transactivation of an AP-1-dependent prom oter. We suggest that signalling through the LFA-1 integrin may affect c-Ju n-driven transcription by regulating JAB1 nuclear localization. This repres ents a new pathway for integrin-dependent modulation of gene expression.