Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw

Annick Verhee

Jan Tavernier

Sven Eyckerman

Joel S Vandekerckhove

Xaveer Van Ostade

Daniel Broekaert

Joël S Vandekerckhove

Wim Waelput

Described is a recombinant receptor comprising an extracellular ligand-binding domain and a cytoplasmic domain that comprises a heterologous bait polypeptide. The recombinant receptor is activated by binding of a ligand to the ligand-binding domain and by binding of a prey polypeptide to the heterologous bait peptide. The invention also discloses a method for detecting compound-compound binding using the recombinant receptor.

Receptor-based interaction trap

The present invention discloses a recombinant receptor comprising an extracellular ligand-binding domain and a cytoplasmic domain that comprises a heterologous bait polypeptide. The recombinant receptor is activated by binding of a ligand to the ligand binding domain and by binding of a prey polypeptide to the heterologous bait peptide. The present invention also discloses a method for detecting compound-compound binding using the recombinant receptor.

Methods of activating a signaling cascade comprising, introducing leptin and/or a cytokine to a receptor complex comprising gp 130, optionally in combination with a compound acting on adenylate cyclase or acting on one or more downstream targets of adenylate cyclase, thereby inducing genes in neuro-endocrine cells or cells of neuro-endocrine origin. Two distinct gene-sets are induced, immediate early response genes (STAT-3, SOCS-3, Metallothionein-II, the serine/threonine kinase Fnk and the rat homologue of MRF-1), and late induced target genes (Pancreatitis Associated Protein I, Squalene Epoxidase, Uridinediphosphate Glucuronyl Transferase and Annexin VIII). Strong co-stimulation with the adenylate cyclase activator forskolin was shown with respect to late induced target genes. Transcripts encoding Leptin Induced Protein I (LIP-I) and Leptin Induced Protein II (LIP-II) were identified; however, no forskolin co-stimulatory effect was observed. It is also demonstrated that leptin modulates in vivo expression of MT-II, Fnk and Pancreatitis Associated Protein I genes.

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Lichtervelde, Belgium

Annick Verhee