The Wnt/β-catenin signaling pathway plays essential roles during development and adult tissue homeostasis. Inappropriate activation of the pathway can result in a variety of malignancies. Protein kinases have emerged as key regulators at multiple steps of the Wnt pathway. In this review, we present a synthesis covering the latest information on how Wnt signaling is regulated by diverse protein kinases.
The Wingless (Wg) pathway represents one of the best-characterized intercellular signaling networks. Studies performed in Drosophila over the last 30 years have contributed to our understanding of the role of Wg signaling in the regulation of tissue growth, polarity, and patterning. These studies have revealed mechanisms conserved in the vertebrate Wnt pathways and illustrate the elegance of using the Drosophila model to understand evolutionarily conserved modes of gene regulation. In this article, we describe the function of Wg signaling in patterning the Drosophila embryonic epidermis and wing imaginal disc. As well, we present an overview of the establishment of the Wg morphogen gradient and discuss the differential modes of Wg-regulated gene expression.
Homeodomain interacting protein kinase (Hipk) is a member of a novel family of serine/threonine kinases. Extensive biochemical studies of vertebrate homologs, particularly Hipk2, have identified a growing list of interactors, including proteins involved in transcriptional regulation, chromatin remodeling and essential signaling pathways such as Wnt and TGFbeta. To gain insight into the in vivo functions of the single Drosophila Hipk we characterized loss of function alleles, which revealed an essential requirement for hipk. We find that in the developing eye, hipk promotes the Notch pathway. Notch signaling acts at multiple points in eye development to promote growth, proliferation and patterning. Hipk stimulates the early function of Notch in promotion of global growth of the eye disc. It has been shown in the Drosophila eye that Hipk interferes with the repressive activity of the global co-repressor, Groucho (Gro). Here, we propose that Hipk antagonizes Gro to promote the transmission of the Notch signal, indicating that Hipk plays numerous roles in regulating gene expression through interference with the formation of Gro-containing co-repressor complexes.
Frizzled/planar cell polarity (PCP) signaling regulates cell motility in several tissues, including ommatidial rotation in Drosophila melanogaster. The Nemo kinase has also been linked to cell motility regulation and ommatidial rotation. The mechanistic role(s) of Nemo during rotation remain however obscure. We demonstrate that nemo functions throughout the entire rotation movement promoting rate of rotation. Genetic and molecular studies indicate that Nemo binds both the core PCP factor complex of Strabismus–Prickle, and the E-cadherin–β-catenin (Armadillo) complex, which colocalize and like Nemo also promote rotation. Strabismus/Vang binds and stabilizes Nemo asymmetrically within the ommatidial precluster. Nemo and β-catenin then act synergistically promoting rotation, which is mediated in vivo through Nemo phosphorylation of β-catenin. Our data suggest that Nemo serves as a conserved molecular link between core PCP factors and E-cad/β-catenin complexes, promoting ommatidial rotation and cell motility in general.
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