Cyclic GMP has been proposed to regulate axonal development, but the molecular and cellular mechanisms underlying the formation of axon branches are not well understood. Here, we report the use of rodent embryonic sensory neurons from the dorsal root ganglion (DRG) to demonstrate the role of cGMP signaling in axon branching and to identify the downstream molecular pathway mediating this novel r...

The WNT signalling pathway controls many developmental processes and plays a key role in maintenance of intestine renewal and homeostasis. Glycogen Synthase Kinase 3 (GSK3) is an important component of the WNT pathway and is involved in regulating β-catenin stability and expression of WNT target genes. The mechanisms underpinning GSK3 regulation in this context are not completely understood, wi...

Canonical Wnt/beta-catenin signaling has central roles in development and diseases, and is initiated by the action of the frizzled (Fz) receptor, its coreceptor LDL receptor-related protein 6 (Lrp6), and the cytoplasmic dishevelled (Dvl) protein. The functional relationships among Fz, Lrp6 and Dvl have long been enigmatic. We demonstrated previously that Wnt-induced Lrp6 phosphorylation via gly...

The prevention of apoptosis is a key function of growth factors in the regulation of erythropoiesis. This study examined the role of the constitutively active serine/threonine kinase glycogen synthase kinase-3 (GSK3), a target of the phosphoinositide-3-kinase (PI3K)/Akt pathway, in the regulation of apoptosis in primary human erythroid progenitors. GSK3 phosphorylation at its key regulatory res...

Glycogen synthase kinase 3 (GSK3) β and α are serine/threonine kinases involved in many biological processes. A primary mechanism of GSK3 activity regulation is phosphorylation of N-terminal serine (S) residues (S9 in GSK3β, S21 in GSK3α). Phosphorylation is inhibitory to GSK3 kinase activity because the phosphorylated N-terminus acts as a competitive inhibitor for primed substrates. Despite wi...

To investigate if glycogen synthase kinase 3 (GSK3) is involved in squamous differentiation of airway (tracheobronchial) epithelial cells, primary pig airway epithelial cells were treated with lithium chloride, a highly selective inhibitor of GSK3. Change in morphology of cells was monitored under microscopy, and expression of beta-catenin, phosphorylated GSK3 and involucrin, a squamous differe...

Signaling by the Wnt family of extracellular proteins is critical in a variety of developmental processes in which cell and tissue polarity are established [1-5]. Wnt signal transduction has been studied mostly by the genetic approach in Drosophila and Caenorhabditis elegans [1,2,5], but the biochemical mechanisms involved remain to be elucidated. The Wnt pathway also operates during axis deter...

Glycogen synthase kinase-3β (GSK3β) is a serine/threonine protein kinase that plays an important role in renal tubular injury and regeneration in acute kidney injury. However, its role in the development of renal fibrosis, often a long-term consequence of acute kidney injury, is unknown. Using a mouse model of renal fibrosis induced by ischemia-reperfusion injury, we demonstrate increased GSK3β...

Glycogen synthase kinase 3 GSK3β participates in a wide variety of functions including regulation of glucose metabolism. It is ubiquitously expressed including epithelial tissues. However, whether GSK3β participates in the regulation of epithelial transport is not known. The present study thus explored whether GSK3β influences the Na(+)-coupled transport of glucose. To this end, SGLT1 was expre...

Two key events in Wnt signal transduction, receptor endocytosis and inactivation of Glycogen Synthase Kinase 3 (GSK3), remain incompletely understood. Taelman et al. (2010) discover that Wnt signaling inactivates GSK3 by sequestering the enzyme in multivesicular bodies, thus linking these two events and providing a new framework for understanding Wnt signaling.