Title:
FUNCTIONAL DOMAIN AND ASSOCIATED MOLECULE OF DOCK2 ESSENTIALLY REQUIRED IN LYMPHOCYTE MIGRATION
Document Type and Number:
WIPO Patent Application WO/2004/048974
Kind Code:
A1
Abstract:
It is intended to provide a method of screening a substance interfering the association of DOCK2 with ELMO1, a method of screening a substance interfering the association of ELMO1 with Tiam1, a method of searching for remedies for immune-related diseases such as allergy, autoimmune diseases, GvH and graft rejection by using these screening methods, etc. It is found out that a DOCK2 mutant lacking 504 amino acid residues at the N-end of DOCK2 shows a remarkably lowered ability to activate Rac and cannot induce actin polymerization. ELMO1 is identified as a molecule binding to this region. It is also found out that DOCK2 is associated with ELMO1 via the SH3 domain. It is furthermore found out that ELMO1 binds to Tiam1 which acts as a Rac-specific GDP/GTP exchange factor (GEF). Thus, it is found out that DOCK 2 recruits Tiam1 via ELMO1 and thus activates Rac.
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Inventors:
FUKUI YOSHINORI (JP)
SASAZUKI TAKEHIKO (JP)
SASAZUKI TAKEHIKO (JP)
Application Number:
PCT/JP2003/014538
Publication Date:
June 10, 2004
Filing Date:
November 14, 2003
Export Citation:
Assignee:
JAPAN SCIENCE & TECH AGENCY (JP)
FUKUI YOSHINORI (JP)
SASAZUKI TAKEHIKO (JP)
FUKUI YOSHINORI (JP)
SASAZUKI TAKEHIKO (JP)
International Classes:
A61K45/00; A61P37/02; A61P37/06; A61P37/08; A61P43/00; C12N15/09; C12N15/12; G01N33/15; G01N33/50; G01N33/564; G01N33/566; (IPC1-7): G01N33/566; G01N33/50; G01N33/15; C12N15/12
Other References:
FUKUI Y. ET AL.: "Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration", NATURE, vol. 412, 23 August 2001 (2001-08-23), pages 826 - 831, XP002977554
MICHIELS F. ET AL.: "A role for Rac in Tiam1-induced membrane ruffling and invasion", NATURE, vol. 375, 25 May 1995 (1995-05-25), pages 338 - 340, XP002039498
GUMIENNY T.L. ET AL.: "CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is rquired for phagocytosis and cell migration", CELL, vol. 107, 5 October 2001 (2001-10-05), pages 27 - 41, XP002977555
NISHIHARA H. ET AL.: "Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1452, 1999, pages 179 - 187, XP004278071
NISHIHARA H. ET AL.: "DOCK2 mediates T-cell receptor-induced activation of Rac2 and IL-2 transcription", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 296, August 2002 (2002-08-01), pages 716 - 720, XP002977556
MICHIELS F. ET AL.: "A role for Rac in Tiam1-induced membrane ruffling and invasion", NATURE, vol. 375, 25 May 1995 (1995-05-25), pages 338 - 340, XP002039498
GUMIENNY T.L. ET AL.: "CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is rquired for phagocytosis and cell migration", CELL, vol. 107, 5 October 2001 (2001-10-05), pages 27 - 41, XP002977555
NISHIHARA H. ET AL.: "Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1452, 1999, pages 179 - 187, XP004278071
NISHIHARA H. ET AL.: "DOCK2 mediates T-cell receptor-induced activation of Rac2 and IL-2 transcription", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 296, August 2002 (2002-08-01), pages 716 - 720, XP002977556
Attorney, Agent or Firm:
Hirota, Masanori (8-5 Akasaka 2-chom, Minato-ku Tokyo, JP)
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