“Protein Kinase Domain Containing, Cytoplasmic (PKDCC) is a protein kinase which has been implicated in longitudinal bone growth through regulation of chondrocytes formation. Nevertheless, the mechanism by which this occurs remains unknown. Here, we identified two new members of the PKDCC family, Pkdcc1 and Pkdcc2 from Xenopus laevis. Interestingly, our knockdown experiments revealed that these two proteins are both involved on blastopore and neural tube closure during gastrula and neurula stages, respectively. In vertebrates, tissue polarity and cell movement observed during gastrulation and neural tube closure are controlled by Wnt/Planar Cell Polarity (PCP) molecular pathway. Our results showed that Pkdcc1 and Pkdcc2 promote the recruitment of Dvl to the plasma membrane. But surprisingly, they revealed different roles in the induction of a luciferase reporter under the control of Atf2 promoter. While Pkdcc1 induces Atf2 expression, Pkdcc2 does not, and furthermore inhibits its normal induction by Wnt11 and Wnt5a. Altogether our data show, for the first time, that members of the PKDCC family are involved in the regulation of JNK dependent Wnt/PCP signaling pathway.”
” both Pkdcc and Gli3 [may] cooperate on the regulation of long bone formation by modulating the temporal kinetics of columnar and hypertrophic chondrocyte domains establishment”
“Pkdcc could also modulate Wnt signaling, since inactivation of Wnt5a also alters the transition between proliferating to hypertrophic chondrocytes. Since Pkdcc regulates protein export from Golgi, its inactivation may directly interfere with either the secretion of the relevant signals or cell-surface localization of receptors ”
“Cell movements are essential for the correct shape of body axis and organ formation during embryo development. These morphogenetic cell movements are not stochastic, they undergo extensive control by distinct signal transduction pathways. One of this pathways is Wnt/Planar Cell Polarity (PCP) signaling pathway that, for example, in polarised tissue, coordinate the morphogenetic processes of the cells in the epithelial sheets plane. A set of core proteins was identified to be involved in PCP pathway, in both vertebrates and invertebrates. In vertebrates this group include the transmembrane receptor Fizzled (Fz), the cytoplasmic molecules Dishevelled (Dvl), Diego (Dgo) and Prickle (Pk), the transmembranar protein VanGogh/Strabismus (Vang/Stbm) and the cadherin-like protein Flamingo/Celsr1 (Fmg/Clsr1). These core PCP components were identified as genes whose inactivation leads to cell polarity mis-alignment. The PCP is involved in the coordination of cells within a tissue sheet, either by direct cell-cell interaction or under the influence of a diffusible ligand-based signalling system [9]. This occurs because these proteins localize in different regions inside the cell: Fz, Dvl and Dgo are localized in the proximal region, Vangl2 and Pk in distal region and Clsr1 localize in both distal and proximal regions, which is essential for the proper establishment of polarization”
“Pkdcc1 and Pkdcc2 promote recruitment of Dishevelled to the plasma membrane through DEP domain”
” Pkdcc1 alone is able to induce the expression of Atf2-luc, and the activation of non-canonical Wnt signaling. Curiously and contrary, Pkdcc2 is not able to activate Atf2 expression, inhibiting the normal activation of JNK dependent non-canonical Wnt downstream of Wnt11 or Wnt5a”