Mice devoid of Fer protein-tyrosine kinase activity are viable and fertilebut display reduced cortactin phosphorylation

The ubiquitous Fer protein-tyrosine kinase has been proposed to regulate di verse processes such as cell growth, cell adhesion, and neurite outgrowth. To gain insight into the biological function of Fer, we have targeted the f er locus with a kinase-inactivating missense mutation (fer(D743R)). Mice ho mozygous for this mutation develop normally, have no overt phenotypic diffe rences 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 i n overall cellularity of bone marrow, spleen, or thymus in the absence of p er activity. While most platelet-derived growth factor (PDGF)-induced tyros ine phosphorylation was unchanged in fer(D743R) homozygous embryonic fibrob lasts, cortactin phosphorylation was reduced. However, Fer kinase activity was not required for PDGF-induced Stat3, p120(ctn), or epidermal growth fac tor (EGF)-induced beta -catenin phosphorylation. Also, no defects were obse rved in changes to the actin cytoskeleton, adherens junctions, or focal adh esions in PDGF- or EGF-stimulated fer(D743R) homozygous embryonic fibroblas ts. Therefore, Fer likely serves a redundant role in regulating cell growth , cell adhesion, retinal development, and spermatogenesis but is required f or efficient phosphorylation of cortactin.