INVESTIGADORES
ARREGUI Carlos Oscar
artículos
Título:
The nonreceptor tyrosine kinase fer mediates cross-talk between N-cadherin and B-Integrins
Autor/es:
CARLOS OSCAR ARREGUI; PATHRE, PURNIMA; LILIEN, JACK; BALSAMO, JANNE
Revista:
JOURNAL OF CELL BIOLOGY
Editorial:
Rockefeller University Press
Referencias:
Año: 2000 vol. 149 p. 1263 - 1273
ISSN:
0021-9525
Resumen:
Cadherins and integrins must function in a
coordinated manner to effectively mediate the cellular
interactions essential for development. We hypothesized
that exchange of proteins associated with their
cytoplasmic domains may play a role in coordinating
function. To test this idea, we used Trojan peptides to
introduce into cells and tissues peptide sequences designed
to compete for the interaction of specific effectors
with the cytoplasmic domain of N-cadherin, and assayed
their effect on cadherin- and integrin-mediated
adhesion and neurite outgrowth. We show that a peptide
mimicking the juxtamembrane (JMP) region of the
cytoplasmic domain of N-cadherin results in inhibition
of N-cadherin and b1-integrin function. The effect of
JMP on b1-integrin function depends on the expression
of N-cadherin and is independent of transcription or
translation. Treatment of cells with JMP results in the
release of the nonreceptor tyrosine kinase Fer from the
cadherin complex and its accumulation in the integrin
complex. A peptide that mimics the first coiled-coil domain
of Fer prevents Fer accumulation in the integrin
complex and reverses the inhibitory effect of JMP.
These findings suggest a new mechanism through which
N-cadherin and b1-integrins are coordinately regulated:
loss of an effector from the cytoplasmic domain
of N-cadherin and gain of that effector by the
b1-integrin complex.
