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J. Cell Biol. 149 (6): 1263-1274

Copyright © 2000 by the Rockefeller University Press.

Original Article

The Nonreceptor Tyrosine Kinase Fer Mediates Cross-Talk between N-Cadherin and β1-Integrins

Carlos Arreguia, Purnima Pathrea, Jack Liliena, , and Janne Balsamoa

a Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202
Department of Biological Sciences, Wayne State University, Detroit, MI 48202.(313) 577-6891(313) 577-0133


Abstract: 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 β1-integrin function. The effect of JMP on β1-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 β1-integrins are coordinately regulated: loss of an effector from the cytoplasmic domain of N-cadherin and gain of that effector by the β1-integrin complex.

Key Words: cadherin • integrin • Trojan peptides • adhesion • neurite outgrowth

The present address of Carlos Arregui is INTECH, Camino Circunvalación Km 6, CC164, 7130 Chascomús, Argentina. The present address of J. Lilien and J. Balsamo is Department of Biological Sciences, University of Iowa, Iowa City, IA 52242-1324.

Abbreviations used in this paper: CBP, catenin binding peptide; COP, control antennapedia peptide; FCC, Fer coiled-coil domain peptide; FNT, Fer NH2-terminal peptide; JMP, juxtamembrane peptide; LN, L cells expressing N-cadherin; SBP, Shc binding region peptide.

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