Pharmacia & Upjohn Aktiebolag

Biovitrum Ab

Staffan Lake

Johan W Stjernschantz

Isabel Climent-Johansson

Karin Dahlman-Wright

Wyeth Wasserman

The present invention is directed to a novel Afx response element comprising the nucleotide sequence AACATGTT, said nucleotide sequence having a DNA binding site for the human fork head transkription factor Afx. The invention also relates to the use of the Afx response element in the screening for genes as diabetes drug targets and in the bioinformatic analysis of the human genome, said genes in turn being useful in other screening methods for compounds modifying the insulin receptor signaling pathway. A further aspect of the invention is a vector construct comprising the novel nucleotide sequence, a host cell transformed with said vector construct as well as the fusion protein expressed by said host cell.

Response element

Molecular cloning and expression of a prostaglandin F2&agr; receptor which is linked to the signal transduction pathways via guanine nucleotide binding regulatory (G) proteins and measured by, for example, cAMP, IP or intracellular calcium. By constructing cell lines that express a prostaglandin F2&agr; receptor, the affinities and efficacies of agonist and antagonist drugs with the receptor can be assessed. A recombinant DNA construct includes a vector and a DNA fragment encoding a prostaglandin F2&agr; receptor. A host cell is transformed with a recombinant DNA construct, so that the DNA fragment is expressed and a prostaglandin F2&agr; receptor is produced. Suitable host systems include eukaryotic and prokaryotic cells, especially mamalian cells such as rat or human. Additionally, for diagnostic purposes, antibodies to a prostaglandin F2&agr; receptor can be prepared by producing all or a portion of the receptor protein and injecting these into various types of mammals. Using the resulting antibodies, expression of an F2&agr; receptor cDNA, i.e. receptor protein in tissue and cells can be measured.

DNA encoding a prostaglandin F2&agr; receptor, a host cell transformed therewith and an expression product thereof

DNA encoding a prostaglandin F28 receptor, a host cell transformed

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Lidingö, Sweden

Staffan Lake