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

Integrin adhesion receptors transduce signals that control complex cell functions which require the regulation of gene expression, such as proliferation, differentiation and survival. Their intracellular domain has no catalytic function, indicating that interaction with other transducing molecules i...

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Bibliographic Details
Published in:Nature (London) 2000-04, Vol.404 (6778), p.617-621
Main Authors: Bianchi, Elisabetta, Denti, Simona, Granata, Alessandra, Bossi, Giovanna, Geginat, Jens, Villa, Antonello, Rogge, Lars, Pardi, Ruggero
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - metabolism
AP-1 protein
Biological and medical sciences
c-Jun protein
Cell Nucleus - metabolism
Cell physiology
Cellular biology
COP9 Signalosome Complex
COS Cells
Cytoplasm - metabolism
DNA-Binding Proteins - metabolism
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation - physiology
Genes
Humans
Intracellular Signaling Peptides and Proteins
JAB1 protein
Jurkat Cells
Luciferases - genetics
Lymphocyte Function-Associated Antigen-1 - metabolism
Membranes
Molecular and cellular biology
Nervous system
Peptide Hydrolases
Protein Binding
Proteins
Receptor Aggregation
Signal Transduction
T-Lymphocytes - metabolism
Transcription Factor AP-1 - metabolism
Transcription Factors - metabolism
Transcription, Genetic
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Summary:Integrin adhesion receptors transduce signals that control complex cell functions which require the regulation of gene expression, such as proliferation, differentiation and survival. Their intracellular domain has no catalytic function, indicating that interaction with other transducing molecules is crucial for integrin-mediated signalling. Here we have identified a protein that interacts with the cytoplasmic domain of the β2 subunit of the αL/β2 integrin LFA-1. This protein is JAB1 (Jun activation domain-binding protein 1), a coactivator of the c-Jun transcription factor. We found that JAB1 is present both in the nucleus and in the cytoplasm of cells and that a fraction of JAB1 colocalizes with LFA-1 at the cell membrane. 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 promoter. We suggest that signalling through the LFA-1 integrin may affect c-Jun-driven transcription by regulating JAB1 nuclear localization. This represents a new pathway for integrin-dependent modulation of gene expression.
ISSN:0028-0836
1476-4687
DOI:10.1038/35007098