INVESTIGADORES
ARREGUI Carlos Oscar
artículos
Título:
PTP1B Modulates the Association of beta -Catenin with N-cadherin through Binding to an Adjacent and Partially Overlapping Target Site.
Autor/es:
XU, G.; CARLOS OSCAR ARREGUI; BALSAMO, JANNE; LILIEN, JACK
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Editorial:
American Society for Biochemistry and Molecular Biology
Referencias:
Año: 2002 vol. 277 p. 49989 - 49997
ISSN:
0021-9258
Resumen:
The nonreceptor tyrosine phosphatase PTP1B associates
with the cytoplasmic domain of N-cadherin and
may regulate cadherin function through dephosphorylation
of b-catenin. We have now identified the domain
on N-cadherin to which PTP1B binds and characterized
the effect of perturbing this domain on cadherin function.
Deletion constructs lacking amino acids 872891
fail to bind PTP1B. This domain partially overlaps with
the b-catenin binding domain. To further define the relationship
of these two sites, we used peptides to compete
in vitro binding. A peptide representing the most
NH2-terminal 8 amino acids of the PTP1B binding site,
the region of overlap with the b-catenin target, effectively
competes for binding of b-catenin but is much less
effective in competing PTP1B, whereas two peptides
representing the remaining 12 amino acids have no effect
on b-catenin binding but effectively compete for
PTP1B binding. Introduction into embryonic chick retina
cells of a cell-permeable peptide mimicking the 8
most COOH-terminal amino acids in the PTP1B target
domain, the region most distant from the b-catenin target
site, prevents binding of PTP1B, increases the pool
of free, tyrosine-phosphorylated b-catenin, and results
in loss of N-cadherin function. N-cadherin lacking this
same region of the PTP1B target site does not associate
with PTP1B or b-catenin and is not efficiently expressed
at the cell surface of transfected L cells. Thus, interaction
of PTP1B with N-cadherin is essential for its association
with b-catenin, stable expression at the cell surface,
and consequently, cadherin function.