Based on their work and that of other laboratories, these investigators propose that hDlg is a component, possibly the essential nucleating agent, of a multi-protein complex of plasma membrane- associated signaling molecules. This hypothesis is based on the observed binding of hDlg sequences to APC, Abl, Crk, Lck, a new putative dual-specificity protein kinase called PBK1 (PDZ-Binding Kinase 1), T/SXV motif channel proteins, SH3-containing proteins, polyproline- containing proteins, and/or protein 4.1 oezrin. The proposed research will test this hypothesis by: (1) refining the map of interaction domains between hDlg and 4.1/ERM proteins and the role of this interaction in targeting to the membrane; (2) quantifying and refining the understanding of hDlg association with itself; (3) quantifying and refining the partners; and (4) assessing the implication of the PDZ- mediated association between hDlg and a putative kinase identified by a yeast two-hybrid screen. The long-term goal is to understand better the mode of action and biochemical characteristics of this tumor suppressor protein.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057314-03
Application #
6180515
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Spalholz, Barbara A
Project Start
1998-05-01
Project End
2002-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
3
Fiscal Year
2000
Total Cost
$276,217
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Gaudet, Suzanne; Langlois, Marie-Josee; Lue, Robert A et al. (2011) The MEK2-binding tumor suppressor hDlg is recruited by E-cadherin to the midbody ring. BMC Cell Biol 12:55