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Molecular and Cellular Biology, October 1998, p. 5762-5770, Vol. 18, No. 10
Section of Molecular Carcinogenesis,
Department of Pathology, Childrens Hospital of Los Angeles Research
Institute and School of Medicine, University of Southern California,
Los Angeles, California 90027
Received 17 February 1998/Returned for modification 26 March
1998/Accepted 15 July 1998
The Fer protein belongs to the fes/fps family of nontransmembrane
receptor tyrosine kinases. Lack of success in attempts to establish a
permanent cell line overexpressing it at significant levels suggested a
strong negative selection against too much Fer protein and pointed to a
critical cellular function for Fer. Using a tetracycline-regulatable
expression system, overexpression of Fer in embryonic fibroblasts was
shown to evoke a massive rounding up, and the subsequent detachment of
the cells from the substratum, which eventually led to cell death.
Induction of Fer expression coincided with increased complex formation
between Fer and the cadherin/src-associated substrate
p120cas and elevated tyrosine phosphorylation
of p120cas.
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Involvement of the Tyrosine Kinase Fer in
Cell Adhesion

-Catenin also exhibited clearly
increased phosphotyrosine levels, and Fer and
-catenin were found to
be in complex. Significantly, although the levels of
-catenin,
-catenin, and E-cadherin were unaffected by Fer overexpression,
decreased amounts of
-catenin and
-catenin were
coimmunoprecipitated with E-cadherin, demonstrating a dissolution of
adherens junction complexes. A concomitant decrease in levels of
phosphotyrosine in the focal adhesion-associated protein p130 was also
observed. Together, these results provide a mechanism for explaining
the phenotype of cells overexpressing Fer and indicate that the Fer
tyrosine kinase has a function in the regulation of cell-cell adhesion.
*
Corresponding author. Mailing address: Section of
Molecular Carcinogenesis, Department of Pathology, MS#103, Childrens
Hospital of Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027. Phone: (323) 669-4595. Fax: (323) 666-0489. E-mail:
heisterk{at}hsc.usc.edu.
Present address: Hubrecht Laboratory, Netherlands Institute for
Developmental Biology, 3584 CT Utrecht, The Netherlands.
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