Titre
A unique set of SH3-SH3 interactions controls IB1 homodimerization.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Kristensen, O.
Auteure/Auteur
Guenat, S.
Auteure/Auteur
Dar, I.
Auteure/Auteur
Allaman-Pillet, N.
Auteure/Auteur
Abderrahmani, A.
Auteure/Auteur
Ferdaoussi, M.
Auteure/Auteur
Roduit, R.
Auteure/Auteur
Maurer, F.
Auteure/Auteur
Beckmann, J.S.
Auteure/Auteur
Kastrup, J.S.
Auteure/Auteur
Gajhede, M.
Auteure/Auteur
Bonny, C.
Auteure/Auteur
Liens vers les unités
ISSN
0261-4189
Statut éditorial
Publié
Date de publication
2006
Volume
25
Numéro
4
Première page
785
Dernière page/numéro d’article
797
Peer-reviewed
Oui
Langue
anglais
Notes
Journal Article Research Support, Non-U.S. Gov't --- Old month value: Feb 22
Résumé
Islet-brain 1 (IB1 or JIP-1) is a scaffold protein that interacts with components of the c-Jun N-terminal kinase (JNK) signal-transduction pathway. IB1 is expressed at high levels in neurons and in pancreatic beta-cells, where it controls expression of several insulin-secretory components and secretion. IB1 has been shown to homodimerize, but neither the molecular mechanisms nor the function of dimerization have yet been characterized. Here, we show that IB1 homodimerizes through a novel and unique set of Src homology 3 (SH3)-SH3 interactions. X-ray crystallography studies show that the dimer interface covers a region usually engaged in PxxP-mediated ligand recognition, even though the IB1 SH3 domain lacks this motif. The highly stable IB1 homodimer can be significantly destabilized in vitro by three individual point mutations directed against key residues involved in dimerization. Each mutation reduces IB1-dependent basal JNK activity in 293T cells. Impaired dimerization also results in a reduction in glucose transporter type 2 expression and in glucose-dependent insulin secretion in pancreatic beta-cells. Taken together, these results indicate that IB1 homodimerization through its SH3 domain has pleiotropic effects including regulation of the insulin secretion process.
PID Serval
serval:BIB_8020128E6107
PMID
Open Access
Oui
Date de création
2008-01-25T15:18:42.014Z
Date de création dans IRIS
2025-05-21T00:03:00Z