Inhibition by Wnt-1 or Wnt-3a of nerve growth factor-induced differentiation of PC12 cells is reversed by bisindolylmaleimide-I but not by several other PKC inhibitors

Chou, Alice H; Howard, Bruce D.

doi:10.1038/sj.onc.1205791

Cited by 14 publications

(11 citation statements)

References 34 publications

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“…Optimedin's action on stimulated PC12 cells in some respects resembles action of Wnt proteins [25][26][27][28]. Similar to optimedin expression, expression of Wnt1 or Wnt3a cDNAs in PC12 cells inhibited NGF-induced differentiation PC12 cells and neurite growth.…”

Section: Optimedin Does Not Stimulate Tcf/lef Signalingmentioning

confidence: 86%

“…Optimedin, similar to some other secreted glycoproteins, may interact with cellular receptor(s) and stimulates or inhibits cellular signaling pathways. Altough optimedin's action on stimulated PC12 cells in some respects resembles action of Wnt proteins [25][26][27][28], optimedin does not stimulate the canonical Wnt pathway through TCF/LEF signaling (Fig. 5).…”

Section: Discussionmentioning

confidence: 99%

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Optimedin induces expression of N-cadherin and stimulates aggregation of NGF-stimulated PC12 cells

Lee

Tomarev

2007

Experimental Cell Research

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Optimedin, also known as olfactomedin 3, belongs to a family of olfactomedin domain-containing proteins. It is expressed in neural tissues and Pax6 is involved in the regulation of its promoter. To study possible effects of optimedin on the differentiation of neural cells, we produced stably transfected PC12 cell lines expressing optimedin under a tetracycline-inducible promoter. Cells expressing high levels of optimedin showed higher growth rates and stronger adhesion to the collagen extracellular matrix as compared with control PC12 cells. After stimulation with nerve growth factor (NGF), optimedin-expressing cells demonstrated elevated levels of N-cadherin, β-catenin, α-catenin, and occludin as compared with stimulated, control PC12 cells. Expression of optimedin induced Ca 2+ -dependent aggregation of NGF-stimulated PC12 cells and this aggregation was blocked by the expression of N-cadherin siRNA. Expression of optimedin also changed the organization of the actin cytoskeleton and inhibited neurite outgrowth in NGF-stimulated PC12 cells. We suggest that expression of optimedin stimulates the formation of adherent and tight junctions on the cell surface and this may play an important role in the differentiation of the brain and retina through the modulation of cytoskeleton organization, cell-cell adhesion and migration.

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Section: Optimedin Does Not Stimulate Tcf/lef Signalingmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Optimedin induces expression of N-cadherin and stimulates aggregation of NGF-stimulated PC12 cells

Lee

Tomarev

2007

Experimental Cell Research

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“…The expression of Wnt-1 or Wnt-3a in PC12 cells inhibits NGF-induced neurite outgrowth (11,47). The effects of targeted inactivation of Wnt-1 and Wnt-3a in mice suggest their critical role in neuronal development, including remodeling of the axon (23).…”

Section: Discussionmentioning

confidence: 99%

Wnt-3a and Dvl Induce Neurite Retraction by Activating Rho-Associated Kinase

Kishida

Yamamoto

Kikuchi

2004

Molecular and Cellular Biology

125

103

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Dvl is a key protein that transmits the Wnt signal to the canonical ␤-catenin pathway and the noncanonical planar cell polarity (PCP) pathway. We studied the roles of Rho-associated kinase (Rho-kinase), which is activated by Dvl in the PCP pathway of mammalian cells. The expression of Dvl-1, Wnt-1, or Wnt-3a activated Rho-kinase in COS cells, and this activation was inhibited by the Rho-binding domain of Rho-kinase. The expression of Dvl-1 in PC12 cells activated Rho and inhibited nerve growth factor (NGF)-induced neurite outgrowth. This inhibition was reversed by a Rho-kinase inhibitor but not by a c-Jun N-terminal kinase inhibitor. Dvl-1 also inhibited serum starvation-dependent neurite outgrowth of N1E-115 cells, and expression of the Rho-binding domain of Rho-kinase reversed this inhibitory activity of Dvl-1. Dvl-1 mutants that did not activate Rho-kinase did not inhibit the neurite outgrowth of N1E-115 cells. Furthermore, the purified Wnt-3a protein activated Rho-kinase and inhibited the NGF-dependent neurite outgrowth of PC12 cells. Wnt-3a-dependent neurite retraction was also prevented by a Rho-kinase inhibitor and a Dvl-1 mutant that suppresses Wnt-3a-dependent activation of Rho-kinase. These results suggest that Wnt-3a and Dvl regulate neurite formation through Rho-kinase and that PC12 and N1E-115 cells are useful for analyzing the PCP pathway.Wnt proteins constitute a large family of cysteine-rich secreted ligands that control development in organisms ranging from nematode worms to mammals (59). Wnt regulates axis formation, organ development, and cellular proliferation, morphology, motility, and fate (40, 46). Binding of the Wnt ligand to its receptors can stimulate several distinct intracellular signaling pathways, including the canonical ␤-catenin and noncanonical planar cell polarity-convergent extension (PCP-CE) pathways. For the activation of these pathways, the common mediator Dvl, which transmits signals from receptors to different effector molecules, is required.Dvl is a cytoplasmic protein that acts downstream of Frizzled (Fz) and is a key protein for regulation of the Wnt signal (56). Three Dvl genes, Dvl-1, -2, and -3, have been isolated from mammals. Dvl homologs are conserved in Drosophila melanogaster (Dishevelled [Dsh]) and Xenopus laevis (Xenopus dishevelled [Xdsh]). All Dvl and Dsh family members contain three highly conserved domains: a DIX domain, a PDZ domain, and a DEP domain. The expression of Dvl in cells induces the accumulation of ␤-catenin in the canonical pathway and the activation of Rho and Rac in the PCP-CE pathway (7,16,17,29,41,46,49). The DIX and PDZ domains are important for the activation of the canonical ␤-catenin pathway, whereas the DEP domain is essential for the activation of the noncanonical PCP-CE pathway.In the canonical pathway, the protein level of free cytoplasmic ␤-catenin is controlled by the Wnt signal (40,46,59

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“…Wnts are secretory proteins of ∼40 kDa that control multiple aspects of development, including the proliferation, fate specification, polarity, and migration of cells 6566. In addition, Chou et al reported that Wnt-1 and Wnt-3a both inhibit NGF-induced neurite outgrowth from PC12 cells 67. These results showed that sensory nerve receptors and neurotrophic markers cooperate with Wnt signals in regulating many biological processes, but the mechanisms of their interaction remain poorly defined in the IVD.…”

Section: Effect Of Degenerative Changes On Intervertebral Disk Cell Smentioning

confidence: 99%

Cell Signaling Pathways Related to Pain Receptors in the Degenerated Disk

Hiyama

Sakai

Mochida

2013

Global Spine Journal

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Many of the causes of low back pain are still unknown; sufficient evidence indicates that both degenerative and mechanical change within the intervertebral disk (IVD) is a relevant factor. This article reviews intracellular signaling pathways related to pain receptors in the degenerated IVD. Several reports have demonstrated the number of nerve fibers in the IVD was increased in degenerated disks. In recent years, some groups have reported that an increase in nerve fibers is associated with the presence of inflammatory mediators and/or neurotrophins in the IVD. Cell signaling events, which are regulated by inflammatory mediators and neurotrophins, must be identified to clarify the mechanism underlying low back pain. Major intracellular signaling pathways (nuclear factor kappa β, mitogen-activated protein kinases, and Wnts) potentially play vital roles in mediating the molecular events responsible for the initiation and progression of IVD degeneration. These signaling pathways may represent therapeutic targets for the treatment of IVD degeneration and its associated back pain.

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Inhibition by Wnt-1 or Wnt-3a of nerve growth factor-induced differentiation of PC12 cells is reversed by bisindolylmaleimide-I but not by several other PKC inhibitors

Cited by 14 publications

References 34 publications

Optimedin induces expression of N-cadherin and stimulates aggregation of NGF-stimulated PC12 cells

Optimedin induces expression of N-cadherin and stimulates aggregation of NGF-stimulated PC12 cells

Wnt-3a and Dvl Induce Neurite Retraction by Activating Rho-Associated Kinase

Cell Signaling Pathways Related to Pain Receptors in the Degenerated Disk

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