A role for CK2alpha/beta in Xenopus early embryonic development.
Journal - Molecular and cellular biochemistry (Netherlands )
CK2 is expressed widely in early embryonic development in several animal models, however its developmental role is unclear. One of the substrates of CK2 that is important in embryonic development is beta-catenin, the transcriptional co-activator of the canonical Wnt signaling pathway. This pathway has been implicated in diverse aspects of embryonic development, including one of the earliest events in embryonic development, the establishment of the dorso-ventral embryonic axis. In Xenopus laevis, dorso-ventral axis formation is dependent upon stabilization of beta-catenin in the future dorsal side of the embryo. Since CK2 phosphorylation of beta-catenin stabilizes it, we hypothesized that CK2 might be critical to upregulation of beta-catenin in Xenopus embryos and to the process of axis establishment. Our results demonstrate that CK2 is required for dorsal axis formation and is for normal upregulation of Wnt signaling genes and targets. Thus, CK2 is a regulator of endogenous axis formation in vertebrates.
|ISSN : ||0300-8177|
|Mesh Heading : ||Animals Casein Kinase II Embryo, Nonmammalian Embryonic Development Phosphorylation Protein Subunits Up-Regulation Wnt Proteins Xenopus laevis beta Catenin enzymology physiology metabolism embryology|
|Mesh Heading Relevant : ||Body Patterning metabolism metabolism metabolism|
CK2 Phosphorylation of the Armadillo Repeat Region of -Catenin Potentiates Wnt Signaling*
Journal - Journal of Biological Chemistry
Protein kinase CK2 is a ubiquitous serine/threonine kinase involvedin many
biological processes. It is overexpressed in many malignanciesincluding
rodent and human breast cancer, and is up-regulatedin Wnt-transfected mammary
epithelial cells, where it can befound in a complex with dishevelled and
-catenin. -Cateninis a substrate for CK2 and inhibition of CK2
reduces levelsof -catenin and dishevelled. Here we report that
inhibitionof CK2 using pharmacologic agents or expression of kinase inactive
subunits reduces -catenin-dependent transcription and proteinlevels in
a proteasome-dependent fashion. The major regionof phosphorylation of
-catenin by CK2 is the central armadillorepeat domain, where carrier
proteins like axin and the adenomatouspolyposis coli gene product
APC interact with -catenin. Themajor CK2 phosphorylation site in this
domain is Thr393, asolvent-accessible residue in a key hinge
region of the molecule.Mutation of this single amino acid reduces
-catenin phosphorylation,cotranscriptional activity, and stability.
Thus, CK2 is a positiveregulator of Wnt signaling through phosphorylation of
-cateninat Thr393, leading to proteasome resistance and
increased proteinand co-transcriptional activity.* This work was supported by National Institutes of Health GrantsES11624 and
CA71796 (to D. C. S.) and a Massachusetts Departmentof Public Health Breast
Cancer Training grant (to D. H. S.).The costs of publication of this article
were defrayed in partby the payment of page charges. This article must
thereforebe hereby marked "advertisement" in accordance
with 18 U.S.C.Section 1734 solely to indicate this fact.