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Molecular and Cellular Biology, October 1998, p. 5762-5770, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Involvement of the Tyrosine Kinase Fer in Cell Adhesion

Roberto Rosato, Jacqueline M. Veltmaat,dagger John Groffen, and Nora Heisterkamp*

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. beta -Catenin also exhibited clearly increased phosphotyrosine levels, and Fer and beta -catenin were found to be in complex. Significantly, although the levels of alpha -catenin, beta -catenin, and E-cadherin were unaffected by Fer overexpression, decreased amounts of alpha -catenin and beta -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.

dagger Present address: Hubrecht Laboratory, Netherlands Institute for Developmental Biology, 3584 CT Utrecht, The Netherlands.

Molecular and Cellular Biology, October 1998, p. 5762-5770, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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