Mice devoid of fer protein-tyrosine kinase activity are viable and fertile but display reduced cortactin phosphorylation.
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 (fer(D743R)). 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 fer(D743R) homozygous embryonic fibroblasts, cortactin phosphorylation was reduced. However, Fer kinase activity was not required for PDGF-induced Stat3, p120(ctn), 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 fer(D743R) 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.
Craig
A W
AW
Department of Biochemistry, Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Zirngibl
R
R
Williams
K
K
Cole
L A
LA
Greer
P A
PA
D000199:Actins / Q000378:metabolism; D000483:Alleles; D000818:Animals; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism; D051356:Cortactin; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005298:Fertility / Q000235:genetics*; D005347:Fibroblasts; D017353:Gene Deletion; D018390:Gene Targeting; D005838:Genotype; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism*; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015996:Survival Rate; D015534:Trans-Activators; D051176:beta Catenin; D000095002:Delta Catenin
D000199:Actins; C495267:CTNNB1 protein, mouse; D051177:Catenins; D015815:Cell Adhesion Molecules; D051356:Cortactin; C495869:Cttn protein, mouse; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051176:beta Catenin; C052602:proto-oncogene protein c-fes-fps; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse