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Title:
PRESENILIN/CRK BINDING POLYPEPTIDES (PCBP) AND METHODS OF USE THEREOF
Document Type and Number:
WIPO Patent Application WO2001066745
Kind Code:
A3
Abstract:
The invention provide Presenilin/Crk binding polypeptides characterized by interacting with Presenilin polypeptides, modulating intracellular calcium mobilization, and redistributing from cytoplasm to membrane in the presence of a Presenilin polypeptide. The Presenilin/Crk binding polypeptides are further characterized by interacting with a Crk polypeptide and by containing at least one SH3 domain. Also provided are isolated nucleic acids encoding Presenilin/Crk binding polypeptides, antibodies that bind to Presenilin/Crk binding polypeptides, expression vectors containing Presenilin/Crk binding polynucleotides and host cells transformed by Presenilin/Crk binding polynucleotides. The invention provides a method for identifying a compound that modulates intracellular calcium mobilization and/or modulates Presenilin/Crk binding protein levels or activity. The invention includes a method of treating a disorder associated with Presenilin/Crk binding protein. Also provided is a method of diagnosis of a subject having or at risk of having a disorder of the nervous system such as Alzheimer's disease.

Inventors:
SCHUBERT DAVID R (US)
KASHIWA ATSUSHI (JP)
KIMURA HIDEO (US)
Application Number:
PCT/US2001/007024
Publication Date:
July 11, 2002
Filing Date:
March 05, 2001
Export Citation:
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Assignee:
SALK INST FOR BIOLOGICAL STUDI (US)
SCHUBERT DAVID R (US)
KASHIWA ATSUSHI (JP)
KIMURA HIDEO (US)
International Classes:
C07K14/47; C12N15/12; A61K48/00; (IPC1-7): C12N15/12; A01K67/027; A61K48/00; C07K14/47; C07K16/18; C12N15/00; G01N33/68
Domestic Patent References:
WO1999016874A11999-04-08
WO1997046678A11997-12-11
Other References:
DATABASE SWISSPROT 1 January 1998 (1998-01-01), NAGASE ET AL: "Prediction of the coding sequences of unidentified human genes.", XP002187374
DATABASE EMBL 2 March 2000 (2000-03-02), BONALDO M ET AL: "Normalization and substraction: two appoaches to facilitate gene discovery", XP002187375
BUXBAUM JOSEPH D ET AL: "Calsenilin: A calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment.", NATURE MEDICINE, vol. 4, no. 10, October 1998 (1998-10-01), pages 1177 - 1181, XP002187372, ISSN: 1078-8956
HASEGAWA HIDEKI ET AL: "DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane.", MOLECULAR AND CELLULAR BIOLOGY, vol. 16, no. 4, 1996, pages 1770 - 1776, XP002187373, ISSN: 0270-7306
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