Enhanced casein kinase II activity during mouse embryogenesis

Abstract

Mouse embryos at various stages of development were used to study the relationship of protein kinase activities with normal embryogenesis. Casein kinase I1 (CKII) activity in developing mouse embryos shows a 3 -4fold activity increase at day 12 of gestation. Together with the CKII activity, increased phosphorylation of a 110-kDa protein is observed. Treatment of the embryo extracts with heparin, a highly specific inhibitor of CKII activity, results in a drastic reduction of the 110-kDa protein phosphorylation indicating that the protein might be a CKIIspecific substrate. Rapidly proliferating mouse tumour cells also show an enhanced CKII activity. Here too, a 110-kDa phosphoprotein was the major phosphoryl acceptor. Partial proteolytic digestion shows that both proteins are identical. Other protein kinases tested (CAMP-and cGMP-dependent protein kinases) only show a basal level of enzyme activity with minor alterations throughout the different stages of embryogenesis investigated.Casein kinase I1 activity in established and experimentally transformed tumour cells has been shown to be enhanced at least 3 -5-fold compared to normal fibroblasts and primary tumour cell cultures [l]. In contrast, other protein kinases, e. g. CAMP-and cGMP-dependent protein kinases, did not show elevated activities. Casein kinase I1 is a well characterized protein kinase which has unique properties such as using ATP as well as GTP as phosphoryl donors. Furthermore this enzyme has been found in almost all eukaryotic organisms so far investigated [2]. Phosphorylation of key proteins of transcription and translation (e. g. topoisomerase I1[3], RNA polymerases I and I1 [4, 51, translational initiation factor eIF-3 [6] and proteins of the RNP particles [7]) from CKII have been shown to occur in vivo and in vitro. However, little information exists concerning the role of this enzyme during normal cell life. The elevated CKII activities observed in rapidly proliferating tumour cell lines led us to search for stages during normal development of an organism where naturally high proliferation rates prevail. This is the case during fetal and embryonic development. There are stages during mouse embryogenesis where the proliferation rate increases 10-fold within 24 h. Since phosphorylation of nuclear proteins (e. g. RNA polymerases I and I1 and topoisomerase 11) has generally been regarded as a means of modulating gene transcription [8, 91, it is feasible to assume that enzymes

Identification of the In Vivo Casein Kinase II Phosphorylation Site within the Homeodomain of the Cardiac Tisue-Specifying Homeobox Gene Product Csx/Nkx2.5

“…CKII activity is regulated temporally and spatially during development (31). The activity of CKII extracted from whole mouse embryos increases three-to fourfold at 12 dpc and decreases to baseline at birth (49). Although the nuclearly localized Csx/Nkx2.5 is constitutively phosphorylated in transfected COS cells and in the neonatal heart, it is possible that this phosphorylation is temporally and spatially regulated during embryonic stages, like the Drosophila homeoprotein Ultrabithorax (21,39).…”

RNA-binding protein nucleolin in disease

“…This activity was linked to nucleolin's influence on cell cycle progression, embryonic development and tumorigenesis. [103][104][105] The proteolytic cleavage of nucleolin into 30-and 72-kDa peptides was also enhanced by CKII. 106 PKC.…”

Molecular cloning of casein kinase II alpha subunit from Dictyostelium discoideum and its expression in the life cycle.

“…A transient increase of casein kinase II activity was found in developing mouse embryos (98) and fetal rat liver (89). The enzyme activity and the expression of its a subunit are high in Caenorhabditis elegans embryos and decrease in subsequent larval stages (47), and expression of the a, a', and 1 subunits is high in early chicken embryos and decreases during embryonic development (80).…”