Wyeth

American Cyanamid Company

American Home Products Corporation

Kathleen H Young

Bradley Alton Ozenberger

Kenneth Rhodes

Andrew T Wood

Sharon J Rosenzweig-Lipson

David S Howland

Mark Cockett

Karen L Marquis

Brendan William Bingham

Robert Mark

Camelia Birsan

Jian Cao

A transgenic rat containing in its genome a nucleotide sequence encoding a Ga subunit protein, which Ga protein subunit is uncoupled from regulation by Regulators of G-Protein Signaling (RGS) proteins, which Gx subunit protein is eventually the dominant-negative G188S mutant of Gax9, which nucleotide sequence is operatively associated with a neuron-specific expression control sequence, wherein the transgenic rat expresses the GA subunit protein in neural cells resulting in extended D-protein coupled receptor signaling mediated by the Ga subunit protein.

Transgenic animal

Methods and compositions for identifying compounds which disrupt the functional interaction of an intracellular receptor region of an &#x3b1;-subunit of a voltage-gated ion channel and an amino-terminal inactivation region of an ion channel protein are disclosed. Compounds that disrupt the functional or binding interaction of these two regions have significant modulatory effects on ion channel activity, and thus are likely to be useful for treating and/or preventing a wide variety of diseases and pathological conditions associated with ion channel dysfunction. Such conditions include, for example, neurological disorders, cardiac diseases, metabolic diseases, tumor-driven diseases, and autoimmune diseases.

Methods for identifying modulators of N-type ion channel inactivation

This invention relates to novel modified host cells which express heterologous fused proteins and methods of screening for test samples having peptide-binding activity; wherein the modified host cell comprises: (a) a gene sequence encoding a heterologous fusion protein; said fusion protein comprising a first peptide of a peptide binding pair, or segment of said first peptide, which is joined to either a DNA binding domain or its corresponding transcriptional activation domain of a transcriptional activation protein; (b) a gene sequence encoding a heterologous fusion protein, said fusion protein comprising a second peptide of the peptide binding pair in (a), or a segment thereof, fused to either a DNA binding domain or its corresponding transcriptional activation domain, whichever one is not employed in (a); (c) a luciferase gene operatively associated with the transcriptional activation protein, or a portion thereof; (d) optionally, a deletion or mutation in the chromosomal DNA of the host cell for the transcriptional activation protein if present in the selected host cell.

Cell systems having specific interaction of peptide binding pairs

This invention relates to modified host cells which express heterologous fused proteins and methods of screening for test samples having peptide binding activity; wherein the modified host cell comprises: (a) a gene sequence encoding a heterologous fusion protein; the fusion protein comprising a first peptide of a peptide binding pair, or segment of the first peptide, which is joined to either a DNA binding domain or its corresponding transcriptional activation domain of a transcriptional activation protein; (b) a gene sequence encoding a heterologous fusion protein, the fusion protein comprising a second peptide of the peptide binding pair in (a), or a segment thereof, fused to either a DNA binding domain or its corresponding transcriptional activation domain, whichever one is not employed in (a); (c) a reporter gene operatively associated with the transcriptional activation protein, or a portion thereof; (d) optionally, a deletion or mutation in the chromosomal DNA of the host cell for the transcriptional activation protein if present in the selected host cell.

The present invention relates, at least in part, to polypeptides which include Bcl-xL binding domains, novel Bcl-xL binding domains of Pablo polypeptides, nucleic acid molecules encoding such polypeptides, and uses thereof. For example, such polypeptides and nucleic acid molecules are useful in modulating apoptosis, particularly in neural cells, as well as in the treatment or prevention of disorders that can benefit from modulation of cell death.

Pablo, a polypeptide that interacts with Bcl-xL, and uses related thereto

This invention relates to novel modified host cells which express heterologous fused proteins and methods of screening for test samples having peptide-binding activity; wherein the modified host cell comprises: (a) a gene sequence encoding a heterologous fusion protein; said fusion protein comprising a first peptide of a peptide binding pair, or segment of said first peptide, which is joined to either a DNA binding domain or its corresponding transcriptional activation domain of a transcriptional activation protein; (b) a gene sequence encoding a heterologous fusion protein, said fusion protein comprising a second peptide of the peptide binding pair in (a), or a segment thereof, fused to either a DNA binding domain or its corresponding transcriptional activation domain, whichever one is not employed in (a); (c) a reporter gene operatively associated with the transcriptional activation protein, or a portion thereof; (d) optionally, a deletion or mutation in the chromosomal DNA of the host cell for the transcriptional activation protein if present in the selected host cell.

A MORT1 gene initially cloned from HeLa cells and identified as a member of the receptor mediated apoptotic pathway, is expressed in the human neuronal cell line, NTERA2. Isolation of the MORT1 from this cell line revealed a transcript isoform that differed from the known MORT1 sequence by a deletion of 21 base pairs (bp 172-192 of the coding sequence). Cloning of MORT1 from adult human brain revealed two isoforms, one similarly deleted for bp 172-192, the other with a basepair substitution, A for G at position 173. Assessment of MORT1 function in a yeast two hybrid system indicates that the deleted and intact forms of MORT1 differ in their capacity to interact with other members of the apoptotic pathway.

Growing community of inventors

Newtown, PA, United States of America

Kathleen H Young