Abstract: The invention relates to a new type of leptin receptor antagonist, which is able to prevent leptin signaling without preventing the binding of leptin to the leptin binding domain. More specifically, the invention relates to the use of a part of the leptin receptor to prevent the leptin-dependent activation of the receptor, and by this the leptin-induced signaling.

Abstract: The present invention relates to an antagonist or inhibitor of leptin signaling via the leptin receptor. The leptin antagonist binds to the leptin receptor, but is unable to induce JAK-STAT signal transduction via the leptin receptor. By binding to the leptin receptor, the leptin antagonist impairs binding of leptin to the leptin receptor and blocks leptin signaling.

Abstract: The invention relates to a new type of leptin receptor antagonist, which is able to prevent leptin signaling without preventing the binding of leptin to the leptin binding domain. More specifically, the invention relates to the use of a part of the leptin receptor to prevent the leptin-dependent activation of the receptor, and by this the leptin-induced signaling.

Abstract: 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.

Abstract: The present invention relates to a functional fragment of a receptor having a function in signaling. Particularly, the present invention relates to a functional fragment of the leptin receptor, involved in SOCS3, CIS and/or Vav signaling.

Abstract: The present invention relates to an antagonist or inhibitor of leptin signaling via the leptin receptor. The leptin antagonist binds to the leptin receptor, but is unable to induce JAK-STAT signal transduction via the leptin receptor. By binding to the leptin receptor, the leptin antagonist impairs binding of leptin to the leptin receptor and blocks leptin signaling.

Abstract: The present invention relates to a recombinant receptor, comprising a ligand-binding domain and a signaling domain that comprises a heterologous bait polypeptide, which receptor is inactivated by binding of a prey polypeptide to the heterologous bait peptide, either in presence or absence of a ligand binding to the ligand-binding domain. The receptor is activated by addition of a compound that disrupts the bait-prey interaction. The present invention also relates to a method of screening compounds that disrupt compound-compound-binding using the recombinant receptor.

Abstract: The present invention relates to a functional fragment of a receptor, important in signaling. Particularly, the present invention relates to a functional fragment of the leptin receptor, involved in SOCS3, CIS and/or Vav signaling.

Abstract: 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.

Abstract: 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.

Abstract: A method for screening compounds for their ability to bind a receptor and/or the screening of compounds that antagonize the binding of a ligand to a receptor. The invention provides an easy and powerful screening method in eukaryotic cells (other than yeast cells), such as insect cells, plant cells or mammalian cells, for ligands of orphan receptors, preferably of the multimerizing receptor type, for unknown ligands of known receptors, preferably multimerizing receptors, and for the genes encoding these ligands.

Abstract: Chimeric polypeptides encoded by a DNA sequence having a first DNA subsequence coding for a fragment of at least one of the .alpha.-and/or .beta.-chain of the human interleukin-5 receptor, and a second DNA subsequence coding for the constant domains of a heavy--or a light-chain of a human immunoglobulin, or a fragment thereof are useful in treating illnesses with demonstrated eosinophilia.

Abstract: Chimeric polypeptides encoded by a DNA sequence having a first DNA subsequence coding for a fragment of at least one of the .alpha.- and/or .beta.-chain of the human interleukin-5 receptor, and a second DNA subsequence coding for the constant domains of a heavy- or a light-chain of a human immunoglobulin, or a fragment thereof are useful in treating illnesses with demonstrated eosinophilia.

Abstract: It is an object of this invention to provide a human Tumor Necrosis Factor mutein or a pharmaceutically acceptable salt thereof characterized in that the TNF sequence is changed by a deletion, insertion, substitution or combinations thereof, of one or more amino acids so that the mutein shows a significant difference between its binding affinity to the human p75-Tumor-Necrosis-Factor-Receptor and to the human p55-Tumor-Necrosis-Factor-Receptor. The invention also includes DNA sequences coding for such muteins, vectors comprising such DNA sequences, host cells transformed with such vectors and a process for the production of such muteins employing such transformed host cells and pharmaceutical compositions containing such muteins and their use for the treatment of illnesses, for example cancer.

Abstract: Chimeric polypeptides encoded by a DNA sequence having a first DNA subsequence coding for a fragment of at least one of the .alpha.- and/or .beta.-chain of the human interleukin-5 receptor, and a second DNA subsequence coding for the constant domains of a heavy- or a light-chain of a human immunoglobulin, or a fragment thereof are useful in treating illnesses with demonstrated eosinophilia.

Abstract: It is an object of this invention to provide a human Tumor Necrosis Factor mutein or a pharmaceutically acceptable salt thereof characterized in that the TNF sequence is changed by a deletion, insertion, substitution or combinations thereof, of one or more amino acids so that the mutein shows a significant difference between its binding affinity to the human p75-Tumor-Necrosis-Factor-Receptor and to the human p55-Tumor-Necrosis-Factor-Receptor. The invention also includes DNA sequences coding for such muteins, vectors comprising such DNA sequences, host cells transformed with such vectors and a process for the production of such muteins employing such transformed host cells and pharmaceutical compositions containing such muteins and their use for the treatment of illnesses, for example cancer.