Minimal mutation of the cytoplasmic tail inhibits the ability of E-cadherin to activate Rac but not phosphatidylinositol 3-kinase - Direct evidence of a role for cadherin-activated Rac signaling in adhesion and contact formation

Goodwin, M., Kovacs, E. M., Thoreson, M. A., Reynolds, A. B. and Yap, A. S. (2003) Minimal mutation of the cytoplasmic tail inhibits the ability of E-cadherin to activate Rac but not phosphatidylinositol 3-kinase - Direct evidence of a role for cadherin-activated Rac signaling in adhesion and contact formation. Journal of Biological Chemistry, 278 23: 20533-20539. doi:10.1074/jbc.M213171200

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ66320_OA.pdf Full text (open access) application/pdf 408.61KB 0

Author Goodwin, M.
Kovacs, E. M.
Thoreson, M. A.
Reynolds, A. B.
Yap, A. S.
Title Minimal mutation of the cytoplasmic tail inhibits the ability of E-cadherin to activate Rac but not phosphatidylinositol 3-kinase - Direct evidence of a role for cadherin-activated Rac signaling in adhesion and contact formation
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2003-01-01
Year available 2003
Sub-type Article (original research)
DOI 10.1074/jbc.M213171200
Open Access Status File (Publisher version)
Volume 278
Issue 23
Start page 20533
End page 20539
Total pages 7
Editor H. Tabor
Place of publication Bethesda
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Subject C1
270105 Cellular Interactions (incl. Adhesion, Matrix, Cell Wall)
780105 Biological sciences
Abstract Classic cadherins are adhesion-activated cell signaling receptors. In particular, homophilic cadherin ligation can directly activate Rho family GTPases and phosphatidylinositol 3-kinase (PI3-kinase), signaling molecules with the capacity to support the morphogenetic effects of these adhesion molecules during development and disease. However, the molecular basis for cadherin signaling has not been elucidated, nor is its precise contribution to cadherin function yet understood. One attractive hypothesis is that cadherin-activated signaling participates in stabilizing adhesive contacts ( Yap, A. S., and Kovacs, E. M. ( 2003) J. Cell Biol. 160, 11-16). We now report that minimal mutation of the cadherin cytoplasmic tail to uncouple binding of p120-ctn ablated the ability of E-cadherin to activate Rac. This was accompanied by profound defects in the capacity of cells to establish stable adhesive contacts, defects that were rescued by sustained Rac signaling. These data provide direct evidence for a role of cadherin-activated Rac signaling in contact formation and adhesive stabilization. In contrast, cadherin-activated PI3-kinase signaling was not affected by loss of p120-ctn binding. The molecular requirements for E-cadherin to activate Rac signaling thus appear distinct from those that stimulate PI3-kinase, and we postulate that p120-ctn may play a central role in the E-cadherin-Rac signaling pathway.
Keyword Biochemistry & Molecular Biology
Rho-family Gtpases
Cell-cell Adhesion
P120 Catenin
Protein-kinase
Actin Cytoskeleton
Beta-catenin
Complex
Association
Junctions
Localization
Q-Index Code C1
Institutional Status UQ

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 87 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 89 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 15 Aug 2007, 12:00:57 EST