Involvement of the tyrosine kinase fer in cell adhesion.
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 p120(cas) and elevated tyrosine phosphorylation of p120(cas). 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.
Rosato
R
R
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, USA.
Veltmaat
J M
JM
Groffen
J
J
Heisterkamp
N
N
D000818:Animals; D017209:Apoptosis; D051177:Catenins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D050719:Crk-Associated Substrate Protein; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050737:Proto-Oncogene Proteins c-crk; D051381:Rats; D050717:Retinoblastoma-Like Protein p130; D013379:Substrate Specificity; D000095002:Delta Catenin
C493841:BCAR1 protein, human; C493843:Bcar1 protein, rat; D051177:Catenins; D015815:Cell Adhesion Molecules; C493872:Crk protein, rat; D050719:Crk-Associated Substrate Protein; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D050717:Retinoblastoma-Like Protein p130; C052602:proto-oncogene protein c-fes-fps; D011505:Protein-Tyrosine Kinases; D000095002:Delta Catenin