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Molecular and Cellular Biology, January 2001, p. 603-613, Vol. 21, No. 2
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.2.603-613.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Mice Devoid of Fer Protein-Tyrosine Kinase Activity Are Viable and Fertile but Display Reduced Cortactin Phosphorylation

Andrew W. B. Craig,1 Ralph Zirngibl,1 Karen Williams,1 Lesley-Ann Cole,1 and Peter A. Greer1,2,*

Department of Biochemistry1 and Department of Pathology,2 Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada K7L 3N6

Received 1 September 2000/Returned for modification 4 October 2000/Accepted 23 October 2000

The ubiquitous Fer protein-tyrosine kinase has been proposed to regulate diverse processes such as cell growth, cell adhesion, and neurite outgrowth. To gain insight into the biological function of Fer, we have targeted the fer locus with a kinase-inactivating missense mutation (ferD743R). Mice homozygous for this mutation develop normally, have no overt phenotypic differences from wild-type mice, and are fertile. Since these mice lack both Fer and the testis-specific FerT kinase activities, these proteins are clearly not essential for development and survival. No differences were observed in overall cellularity of bone marrow, spleen, or thymus in the absence of Fer activity. While most platelet-derived growth factor (PDGF)-induced tyrosine phosphorylation was unchanged in ferD743R homozygous embryonic fibroblasts, cortactin phosphorylation was reduced. However, Fer kinase activity was not required for PDGF-induced Stat3, p120ctn, or epidermal growth factor (EGF)-induced beta -catenin phosphorylation. Also, no defects were observed in changes to the actin cytoskeleton, adherens junctions, or focal adhesions in PDGF- or EGF-stimulated ferD743R homozygous embryonic fibroblasts. Therefore, Fer likely serves a redundant role in regulating cell growth, cell adhesion, retinal development, and spermatogenesis but is required for efficient phosphorylation of cortactin.

* Corresponding author. Mailing address: Botterell Hall Room A309, Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada K7L 3N6. Phone: (613) 533-2813. Fax: (613) 533-6830. E-mail: greerp{at}post.queensu.ca.

Molecular and Cellular Biology, January 2001, p. 603-613, Vol. 21, No. 2
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.2.603-613.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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