Multiple signaling pathways are involved in the regulation of IGF-I receptor inhibition of PTEN-enhanced apoptosis

Yiping Wu; Michael Karas; Joelle Dupont; Hong Zhao; Yuka Toyoshima; Derek Le Roith

doi:10.1016/j.ghir.2003.08.003

Multiple signaling pathways are involved in the regulation of IGF-I receptor inhibition of PTEN-enhanced apoptosis

Yiping Wu, Michael Karas, Joelle Dupont, Hong Zhao, Yuka Toyoshima, Derek Le Roith

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

PTEN is a dual protein and lipid phosphatase that dephosphorylates PIP3 at the 3′ position, thereby antagonizing PI3-kinase activity. A reduction in PI3′kinase activity enhances the susceptibility of cells to apoptosis. By stably transfecting PC12 cells with an antisense PTEN construct, endogenous PTEN protein levels were reduced by ∼50% and etoposide-induced apoptosis was markedly decreased. Furthermore, IGF-I receptor abrogation of this apoptotic effect was inhibited by both PI3′kinase and by specific inhibitors of p38 MAP kinase. Thus, we show for the first time that p38 MAP kinase is involved in this process. Published by Elsevier Ltd.

Original language	English
Pages (from-to)	52-58
Number of pages	7
Journal	Growth Hormone and IGF Research
Volume	14
Issue number	1
DOIs	https://doi.org/10.1016/j.ghir.2003.08.003
State	Published - Feb 2004
Externally published	Yes

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title = "Multiple signaling pathways are involved in the regulation of IGF-I receptor inhibition of PTEN-enhanced apoptosis",

abstract = "PTEN is a dual protein and lipid phosphatase that dephosphorylates PIP3 at the 3′ position, thereby antagonizing PI3-kinase activity. A reduction in PI3′kinase activity enhances the susceptibility of cells to apoptosis. By stably transfecting PC12 cells with an antisense PTEN construct, endogenous PTEN protein levels were reduced by ∼50% and etoposide-induced apoptosis was markedly decreased. Furthermore, IGF-I receptor abrogation of this apoptotic effect was inhibited by both PI3′kinase and by specific inhibitors of p38 MAP kinase. Thus, we show for the first time that p38 MAP kinase is involved in this process. Published by Elsevier Ltd.",

author = "Yiping Wu and Michael Karas and Joelle Dupont and Hong Zhao and Yuka Toyoshima and {Le Roith}, Derek",

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AU - Wu, Yiping

AU - Karas, Michael

AU - Dupont, Joelle

AU - Zhao, Hong

AU - Toyoshima, Yuka

AU - Le Roith, Derek

PY - 2004/2

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N2 - PTEN is a dual protein and lipid phosphatase that dephosphorylates PIP3 at the 3′ position, thereby antagonizing PI3-kinase activity. A reduction in PI3′kinase activity enhances the susceptibility of cells to apoptosis. By stably transfecting PC12 cells with an antisense PTEN construct, endogenous PTEN protein levels were reduced by ∼50% and etoposide-induced apoptosis was markedly decreased. Furthermore, IGF-I receptor abrogation of this apoptotic effect was inhibited by both PI3′kinase and by specific inhibitors of p38 MAP kinase. Thus, we show for the first time that p38 MAP kinase is involved in this process. Published by Elsevier Ltd.

AB - PTEN is a dual protein and lipid phosphatase that dephosphorylates PIP3 at the 3′ position, thereby antagonizing PI3-kinase activity. A reduction in PI3′kinase activity enhances the susceptibility of cells to apoptosis. By stably transfecting PC12 cells with an antisense PTEN construct, endogenous PTEN protein levels were reduced by ∼50% and etoposide-induced apoptosis was markedly decreased. Furthermore, IGF-I receptor abrogation of this apoptotic effect was inhibited by both PI3′kinase and by specific inhibitors of p38 MAP kinase. Thus, we show for the first time that p38 MAP kinase is involved in this process. Published by Elsevier Ltd.

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M3 - Article

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SN - 1096-6374

VL - 14

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EP - 58

JO - Growth Hormone and IGF Research

JF - Growth Hormone and IGF Research

IS - 1

ER -

Multiple signaling pathways are involved in the regulation of IGF-I receptor inhibition of PTEN-enhanced apoptosis

Abstract

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