Protein kinase VRK-1 and its role in cell proliferation and differentiation

Abstract

VRK-1 (vaccinia-related kinase 1) is a conserved protein kinase that in C. elegans plays critical roles in development of the vulva and the uterus, as well as in normal germ cell proliferation. In mammals, loss of VRK-1 substrates include chromatin proteins histone H2A and BAF and transcription factors p53, c-Jun and ATF2. However, it is not clear whether these proteins are responsible for the phenotypes observed upon loss of VRK-1. Our objective is therefore to more thoroughly characterize the role of VRK-1 in C. elegans development. Using MosSCI we have generatd several transgenic strains that show the expression of VRK-1 not only in previously reported cells (neurons, hypodermal cells and vulva precursos cells), but also in the anchor cell (AC), that plays an essential role in vulval development. Moreover, we find that proper nuclear localization of VRK-1 depends on its C-terminus and is independent from kinase activity. We previosly showed that the timing of AC invasion and localization of actin-binding protein moeABD are affected in vrk-1 mutants. We report here that other markers of polarization (phospholipase C-delta, UNC-6, UNC-40, PAT-3, MIG-2) are unaffected, but they reveal dramatic alterations in AC morphology and contact to uterine cells. During vulval development AC fuses with uterine cells to form utse. Since AC is correctly specified in vrk-1 mutants, we decided to concentrate on uterine cells and our preliminary findings suggest that proliferation and differentiation are severely affected very early in uterine development.