The regulation of cadherin-mediated adhesion by tyrosine phosphorylation/dephosphorylation of β-catenin

Lilien, Jack; Balsamo, Janne

doi:10.1016/j.ceb.2005.08.009

Cited by 426 publications

(424 citation statements)

References 51 publications

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“…Downregulation of cell adhesion is in part achieved by phosphorylation of b-catenin, which promotes the release of b-catenin from the adhesion complex and activates b-catenin nuclear signaling. 2 Several cytoplasmic tyrosine kinases and growth factor-activated receptor tyrosine kinases (RTK) phosphorylate b-catenin, thus promoting a migratory phenotype. [3][4][5] Dynamic regulation by tyrosine phosphatases counteracts b-catenin phosphorylation.…”

Section: Introductionmentioning

confidence: 99%

Nuclear phosphorylated Y142 β-catenin accumulates in astrocytomas and glioblastomas and regulates cell invasion

et al. 2015

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Glioblastoma multiforme (GBM) is a fast growing brain tumor characterized by extensive infiltration into the surrounding tissue and one of the most aggressive cancers. GBM is the most common glioma (originating from glialderived cells) that either evolves from a low grade astrocytoma or appears de novo. Wnt/b-catenin and Hepatocyte Growth Factor (HGF)/c-Met signaling are hyperactive in human gliomas, where they regulate cell proliferation, migration and stem cell behavior. We previously demonstrated that b-catenin is phosphorylated at Y142 by recombinant c-Met kinase and downstream of HGF signaling in neurons. Here we studied phosphoY142 (PY142) b-catenin and dephospho S/T b-catenin (a classical Wnt transducer) in glioma biopsies, GBM cell lines and biopsyderived glioma cell cultures. We found that PY142 b-catenin mainly localizes in the nucleus and signals through transcriptional activation in GBM cells. Tissue microarray analysis confirmed strong nuclear PY142 b-catenin immunostaining in astrocytoma and GBM biopsies. By contrast, active b-catenin showed nuclear localization only in GBM samples. Western blot analysis of tumor biopsies further indicated that PY142 and active b-catenin accumulate independently, correlating with the expression of Snail/Slug (an epithelial-mesenchymal transition marker) and Cyclin-D1 (a regulator of cell cycle progression), respectively, in high grade astrocytomas and GBMs. Moreover, GBM cells stimulated with HGF showed increasing levels of PY142 b-catenin and Snail/Slug. Importantly, the expression of mutant Y142F b-catenin decreased cell detachment and invasion induced by HGF in GBM cell lines and biopsy-derived cell cultures. Our results identify PY142 b-catenin as a nuclear b-catenin signaling form that downregulates adhesion and promotes GBM cell invasion.

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Section: Introductionmentioning

confidence: 99%

Nuclear phosphorylated Y142 β-catenin accumulates in astrocytomas and glioblastomas and regulates cell invasion

et al. 2015

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“…It was recently discovered that BDNF promotes splitting of synaptic vesicle clusters, and this activity depends on dissociation of cadherin-β-catenin complexes [18]. Tyrosine phosphorylation of β-catenin is required for dissociation from cadherins [22], and when this is blocked BDNF-mediated vesicle cluster splitting and synapse formation is prevented. Interestingly, tyrosine phosphorylation of β-catenin also regulates cadherin interactions in the postsynaptic compartment and influences synaptic structure [16].…”

Section: Catenins and The Presynapsementioning

confidence: 99%

Catenins: playing both sides of the synapse

Kwiatkowski

Weis

Nelson

2007

Current Opinion in Cell Biology

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Synapses of the central nervous system (CNS) are specialized cell-cell junctions that mediate intercellular signal transmission from one neuron to another. The directional nature of signal relay requires that synaptic contacts are morphologically asymmetric with distinct protein components, while changes in synaptic communication during neural network formation require synapses to be plastic. Synapse morphology and plasticity require a dynamic actin cytoskeleton. Classical cadherins, which are junctional proteins associated with the actin cytoskeleton, localize to synapses and regulate synaptic adhesion, stability and remodeling. The major intracellular components of cadherin junctions are the catenin proteins, and increasing evidence suggests that cadherin-catenin complexes modulate an array of synaptic processes. Here we review the role of catenins in regulating the development of pre-and postsynaptic compartments and function in synaptic plasticity, with particular focus on their role in regulating the actin cytoskeleton.

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“…Likewise, the issue whether, for example, M-, N-and R-cadherin are all expressed in one homogeneous set of granule cells, or whether there exist, among differentiating granule cells, subsets distinguishable by quantitative differences in their expression of these and/or other cadherins may be approached by fully exploiting the multi-parametric potential of flow cytometry. The approach exemplified here should also permit, in developmentally characterized cells, a correlation to be made between cadherin expression and the expression/activation of cadherin signal processing pathways, known to be critical to cadherin adhesive strength (Lilien and Balsamo, 2005).…”

Section: Some Limitations Of the Current Approach And Further Perspecmentioning

confidence: 99%

Expression of classical cadherins in the cerebellar anlage: Quantitative and functional aspects

Gliem

Weisheit

Mertz

et al. 2006

Molecular and Cellular Neuroscience

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During central nervous system (CNS) development, cell migration precedes and is key to the integration of diverse sets of cells. Mechanistically, CNS histogenesis is realized through a balanced interplay of cell-cell and cell-matrix adhesion molecules. Here, we summarize experiments that probe the developmental expression and potential significance of a set of cadherins, including M-, N and R-cadherin, for patterning of the cerebellar cortex. We established a transgenic marker that allows cerebellar granule cells to be followed from the neuroblast stage to their final, postmitotic settlement. In conjunction with flow-cytometry, this allowed us to derive a quantitative view of cadherin expression in differentiating granule cells and relate it to the expression of the same cadherins in cerebellar inhibitory interneuronal precursors. In vitro reaggregation analysis supports a role for cadherins in cell sorting and migration within the nascent cerebellar cortex that may be rationalized within the context of the differential adhesion hypothesis (Foty and Steinberg, 2005).

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The regulation of cadherin-mediated adhesion by tyrosine phosphorylation/dephosphorylation of β-catenin

Cited by 426 publications

References 51 publications

Nuclear phosphorylated Y142 β-catenin accumulates in astrocytomas and glioblastomas and regulates cell invasion

Nuclear phosphorylated Y142 β-catenin accumulates in astrocytomas and glioblastomas and regulates cell invasion

Catenins: playing both sides of the synapse

Expression of classical cadherins in the cerebellar anlage: Quantitative and functional aspects

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