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 is crucial for integrin-mediated signalling. Here we have identified a protein that interacts with the cytoplasmic domain of the beta2 subunit of the alphaL/beta2 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.
Bianchi
E
E
Scientific Institute San Raffaele-DIBIT, Milano, Italy. bianchi.elisabetta@hsr.it
Denti
S
S
Granata
A
A
Bossi
G
G
Geginat
J
J
Villa
A
A
Rogge
L
L
Pardi
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000075686:COP9 Signalosome Complex; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D010447:Peptide Hydrolases; D011485:Protein Binding; D011940:Receptor Aggregation; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D008156:Luciferases; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex