|
|
|
|
|
|
|
||
J. Cell Biol.,
Volume 143, Number 2, October 19, 1998 523-532
Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202
Cadherin-mediated adhesion depends on the
association of its cytoplasmic domain with the actin-containing cytoskeleton. This interaction is mediated
by a group of cytoplasmic proteins: 
-and 
- or 
- catenin. Phosphorylation of -catenin on tyrosine residues plays a role in controlling this association and, therefore, cadherin function. Previous work from our laboratory suggested that a nonreceptor protein tyrosine
phosphatase, bound to the cytoplasmic domain of
N-cadherin, is responsible for removing tyrosine-bound
phosphate residues from -catenin, thus maintaining
the cadherin-actin connection ().
Here we report the molecular cloning of the cadherin-associated tyrosine phosphatase and identify it as PTP1B. To definitively establish a causal relationship
between the function of cadherin-bound PTP1B and
cadherin-mediated adhesion, we tested the effect of
expressing a catalytically inactive form of PTP1B in
L cells constitutively expressing N-cadherin. We find that expression of the catalytically inactive PTP1B results in reduced cadherin-mediated adhesion. Furthermore, cadherin is uncoupled from its association with
actin, and -catenin shows increased phosphorylation
on tyrosine residues when compared with parental cells
or cells transfected with the wild-type PTP1B. Both the transfected wild-type and the mutant PTP1B are found
associated with N-cadherin, and recombinant mutant
PTP1B binds to N-cadherin in vitro, indicating that the
catalytically inactive form acts as a dominant negative,
displacing endogenous PTP1B, and rendering cadherin
nonfunctional. Our results demonstrate a role for
PTP1B in regulating cadherin-mediated cell adhesion.
-catenin;
cadherin;
protein tyrosine
phosphatase;
cell-cell adhesion
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
