PKN2 is essential for mouse embryonic development and proliferation of mouse fibroblasts

Abstract

PKN 2, a member of the protein kinase N ( PKN ) family, has been suggested by in vitro culture cell experiments to bind to Rho/Rac GTP ases and contributes to cell–cell contact and cell migration. To unravel the in vivo physiological function of PKN 2, we targeted the PKN 2 gene. Constitutive disruption of the mouse PKN 2 gene resulted in growth retardation and lethality before embryonic day (E) 10.5. PKN 2 −/− embryo did not undergo axial turning and showed insufficient closure of the neural tube. Mouse embryonic fibroblasts ( MEF s) derived from PKN 2 −/− embryos at E9.5 failed to grow. Cre‐mediated ablation of PKN 2 in PKN 2 flox/flox MEF s obtained from E14.5 embryos showed impaired cell proliferation, and cell cycle analysis of these MEF s showed a decrease in S‐phase population. Our results show that PKN 2 is essential for mouse embryonic development and cell‐autonomous proliferation of primary MEF s in culture. Comparison of the PKN 2 −/− phenotype with the phenotypes of PKN 1 and PKN 3 knockout strains suggests that PKN 2 has distinct nonredundant functions in vivo , despite the structural similarity and evolutionary relationship among the three isoforms.