Human DKK3 blocking peptide

In the present work, the expression patterns of the Wnt antagonists of the Dickkopf (Dkk) family were characterized in the developing mouse forebrain. In situ hybridisation on sections from E12 embryos showed an expression of dkk2 in the thalamus and dkk3 in the cortical hem and thalamus. At later developmental stages (E15.5, E17.5, and P0), little or no expression of dkk1, dkk2, and dkk4 was found in the forebrain, while dkk3 expression was detected in the ventricular zone (VZ) of the lateral and III ventricles, cortical neurons, migrating cells of the primary and secondary dentate migration, and the neuroblastic layer of the eye. In the adult forebrain, dkk3 expression was detected in the lateral VZ, pyramidal neurons of the hippocampus, and cortical neurons. We also provide evidence indicating that only dkk1 and dkk4, along with two other Wnt antagonists axin2 and wif1, but not dkk2 and dkk3, are involved in a feedback mechanism to restrain Wnt signalling in transgenic mice carrying a conditional augmentation of beta-catenin in the forebrain. (C) 2004 Elsevier B.V. All rights reserved.

Wnt signaling regulates essential biological processes ranging from embryogenesis to neurodegeneration. Recently, we demonstrated that Dickkopf3 (Dkk3) is a pro-survival glycoprotein that positively modulates Wnt signaling. An important step in understanding the mechanism of action of Dkk3 is identifying its interacting proteins in the Wnt pathway. In this study, we used a series of biochemical and functional assays to investigate the interaction between Dkk3 and the Wnt pathway receptors Kremen1 (Krm 1), Kremen 2 (Krm2) and low-density lipoprotein receptor-related protein 6 (LRP6). Here, we report that, contrary to previous studies, Dkk3 interacts with Krm1 and Krm2. However, Dkk3 did not interact with, or alter expression of, LRP6. Blocking protein glycosylation did not alter the interaction between Dkk3 and Krm proteins. Additionally, Krm2 abolished Dkk3-mediated potentiation of Wnt signaling. Therefore, our data establish that Krm proteins are novel binding partners of Dkk3 and suggest a mechanism by which Dkk3 potentiates Wnt signaling.