H-Ras activation Promotes Cytoplasmic Accumulation and Phosphoinositide 3-Oh Kinase Association of β-Catenin in Epidermal Keratinocytes

Research output: Contribution to journal › Journal article › Research › peer-review

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H-Ras activation Promotes Cytoplasmic Accumulation and Phosphoinositide 3-Oh Kinase Association of β-Catenin in Epidermal Keratinocytes. / Espada, Jesús; Pérez-Moreno, Mirna; Braga, Vania M. M.; Rodriguez-Viciana, Pablo; Cano, Amparo.

In: Journal of Cell Biology, Vol. 146, No. 5, 1999, p. 967-980.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Espada, J, Pérez-Moreno, M, Braga, VMM, Rodriguez-Viciana, P & Cano, A 1999, 'H-Ras activation Promotes Cytoplasmic Accumulation and Phosphoinositide 3-Oh Kinase Association of β-Catenin in Epidermal Keratinocytes', Journal of Cell Biology, vol. 146, no. 5, pp. 967-980. https://doi.org/10.1083/jcb.146.5.967

APA

Espada, J., Pérez-Moreno, M., Braga, V. M. M., Rodriguez-Viciana, P., & Cano, A. (1999). H-Ras activation Promotes Cytoplasmic Accumulation and Phosphoinositide 3-Oh Kinase Association of β-Catenin in Epidermal Keratinocytes. Journal of Cell Biology, 146(5), 967-980. https://doi.org/10.1083/jcb.146.5.967

Vancouver

Espada J, Pérez-Moreno M, Braga VMM, Rodriguez-Viciana P, Cano A. H-Ras activation Promotes Cytoplasmic Accumulation and Phosphoinositide 3-Oh Kinase Association of β-Catenin in Epidermal Keratinocytes. Journal of Cell Biology. 1999;146(5):967-980. https://doi.org/10.1083/jcb.146.5.967

Author

Espada, Jesús ; Pérez-Moreno, Mirna ; Braga, Vania M. M. ; Rodriguez-Viciana, Pablo ; Cano, Amparo. / H-Ras activation Promotes Cytoplasmic Accumulation and Phosphoinositide 3-Oh Kinase Association of β-Catenin in Epidermal Keratinocytes. In: Journal of Cell Biology. 1999 ; Vol. 146, No. 5. pp. 967-980.

Bibtex

@article{b33c8d6c8dea476b8b5d67c7ec8befc2,
title = "H-Ras activation Promotes Cytoplasmic Accumulation and Phosphoinositide 3-Oh Kinase Association of β-Catenin in Epidermal Keratinocytes",
abstract = "The mechanisms underlying downregulation of the cadherin/catenin complexes and beta-catenin signaling during tumor progression are not fully understood. We have analyzed the effect of oncogenic H-Ras on E-cadherin/catenin complex formation/stabilization and beta-catenin distribution in epidermal keratinocytes. Microinjection or stable expression of V12Ras into keratinocytes promotes the loss of E-cadherin and alpha-catenin and relocalization of beta-catenin to the cytoplasm and nucleus. Moreover, these effects are dependent on PI3K (phosphoinositide 3-OH kinase) activity. Interestingly, a strong association of p85alpha and p110alpha subunits of PI3K with beta-catenin is induced in V12Ras-expressing keratinocytes, and in vitro binding assays show a direct interaction between beta-catenin and p85alpha. Overexpression of either V12Ras or constitutively active p110alpha induces metabolic stabilization of beta-catenin and promotes its accumulation in cytoplasmic and nuclear pools. In addition, the interaction of beta-catenin with the adenomatous polyposis coli protein is blocked in V12Ras and p110alpha transformants though no changes in glycogen synthase kinase 3 beta activity could be detected. Nevertheless, in V12Ras transformants the in vivo phosphorylation of beta-catenin in Ser residues is strongly decreased. These results indicate that H-Ras activation induces the relocalization and cytoplasmic stabilization of beta-catenin by a mechanism involving its interaction with PI3K.",
keywords = "Adenomatous Polyposis Coli Protein, Animals, Cadherins, Calcium-Calmodulin-Dependent Protein Kinases, Cell Line, Cell Membrane, Cell Nucleus, Cell Transformation, Neoplastic, Cytoplasm, Cytoskeletal Proteins, Enzyme Activation, Glycogen Synthase Kinase 3, Glycogen Synthase Kinases, Keratinocytes, Mice, Microinjections, Oncogene Protein p21(ras), Phosphatidylinositol 3-Kinases, Phosphorylation, Phosphoserine, Phosphotyrosine, Protein Binding, Trans-Activators, alpha Catenin, beta Catenin, Journal Article, Research Support, Non-U.S. Gov't",
author = "Jes{\'u}s Espada and Mirna P{\'e}rez-Moreno and Braga, {Vania M. M.} and Pablo Rodriguez-Viciana and Amparo Cano",
year = "1999",
doi = "10.1083/jcb.146.5.967",
language = "English",
volume = "146",
pages = "967--980",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "5",

}

RIS

TY - JOUR

T1 - H-Ras activation Promotes Cytoplasmic Accumulation and Phosphoinositide 3-Oh Kinase Association of β-Catenin in Epidermal Keratinocytes

AU - Espada, Jesús

AU - Pérez-Moreno, Mirna

AU - Braga, Vania M. M.

AU - Rodriguez-Viciana, Pablo

AU - Cano, Amparo

PY - 1999

Y1 - 1999

N2 - The mechanisms underlying downregulation of the cadherin/catenin complexes and beta-catenin signaling during tumor progression are not fully understood. We have analyzed the effect of oncogenic H-Ras on E-cadherin/catenin complex formation/stabilization and beta-catenin distribution in epidermal keratinocytes. Microinjection or stable expression of V12Ras into keratinocytes promotes the loss of E-cadherin and alpha-catenin and relocalization of beta-catenin to the cytoplasm and nucleus. Moreover, these effects are dependent on PI3K (phosphoinositide 3-OH kinase) activity. Interestingly, a strong association of p85alpha and p110alpha subunits of PI3K with beta-catenin is induced in V12Ras-expressing keratinocytes, and in vitro binding assays show a direct interaction between beta-catenin and p85alpha. Overexpression of either V12Ras or constitutively active p110alpha induces metabolic stabilization of beta-catenin and promotes its accumulation in cytoplasmic and nuclear pools. In addition, the interaction of beta-catenin with the adenomatous polyposis coli protein is blocked in V12Ras and p110alpha transformants though no changes in glycogen synthase kinase 3 beta activity could be detected. Nevertheless, in V12Ras transformants the in vivo phosphorylation of beta-catenin in Ser residues is strongly decreased. These results indicate that H-Ras activation induces the relocalization and cytoplasmic stabilization of beta-catenin by a mechanism involving its interaction with PI3K.

AB - The mechanisms underlying downregulation of the cadherin/catenin complexes and beta-catenin signaling during tumor progression are not fully understood. We have analyzed the effect of oncogenic H-Ras on E-cadherin/catenin complex formation/stabilization and beta-catenin distribution in epidermal keratinocytes. Microinjection or stable expression of V12Ras into keratinocytes promotes the loss of E-cadherin and alpha-catenin and relocalization of beta-catenin to the cytoplasm and nucleus. Moreover, these effects are dependent on PI3K (phosphoinositide 3-OH kinase) activity. Interestingly, a strong association of p85alpha and p110alpha subunits of PI3K with beta-catenin is induced in V12Ras-expressing keratinocytes, and in vitro binding assays show a direct interaction between beta-catenin and p85alpha. Overexpression of either V12Ras or constitutively active p110alpha induces metabolic stabilization of beta-catenin and promotes its accumulation in cytoplasmic and nuclear pools. In addition, the interaction of beta-catenin with the adenomatous polyposis coli protein is blocked in V12Ras and p110alpha transformants though no changes in glycogen synthase kinase 3 beta activity could be detected. Nevertheless, in V12Ras transformants the in vivo phosphorylation of beta-catenin in Ser residues is strongly decreased. These results indicate that H-Ras activation induces the relocalization and cytoplasmic stabilization of beta-catenin by a mechanism involving its interaction with PI3K.

KW - Adenomatous Polyposis Coli Protein

KW - Animals

KW - Cadherins

KW - Calcium-Calmodulin-Dependent Protein Kinases

KW - Cell Line

KW - Cell Membrane

KW - Cell Nucleus

KW - Cell Transformation, Neoplastic

KW - Cytoplasm

KW - Cytoskeletal Proteins

KW - Enzyme Activation

KW - Glycogen Synthase Kinase 3

KW - Glycogen Synthase Kinases

KW - Keratinocytes

KW - Mice

KW - Microinjections

KW - Oncogene Protein p21(ras)

KW - Phosphatidylinositol 3-Kinases

KW - Phosphorylation

KW - Phosphoserine

KW - Phosphotyrosine

KW - Protein Binding

KW - Trans-Activators

KW - alpha Catenin

KW - beta Catenin

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1083/jcb.146.5.967

DO - 10.1083/jcb.146.5.967

M3 - Journal article

C2 - 10477752

VL - 146

SP - 967

EP - 980

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 5

ER -

ID: 188368980