CH-ILKBP regulates cell survival by facilitating the membrane translocation of protein kinase B/Akt

CH-ILKBP regulates cell survival by facilitating the membrane translocation of protein kinase B/Akt

Cell survival depends on proper propagation of protective signals through intracellular signaling intermediates. We report here that calponin homology domain–containing integrin-linked kinase (ILK)–binding protein (CH-ILKBP), a widely expressed adaptor protein localized at plasma membrane-actin junc...

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Main Authors: Fukuda, Tomohiko, Guo, Lida, Shi, Xiaohua, Wu, Chuanyue
Format: Online
Language:English
Published: The Rockefeller University Press 2003
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172761/
id pubmed-2172761
recordtype oai_dc
spelling pubmed-21727612008-05-01 CH-ILKBP regulates cell survival by facilitating the membrane translocation of protein kinase B/Akt Fukuda, Tomohiko Guo, Lida Shi, Xiaohua Wu, Chuanyue Report Cell survival depends on proper propagation of protective signals through intracellular signaling intermediates. We report here that calponin homology domain–containing integrin-linked kinase (ILK)–binding protein (CH-ILKBP), a widely expressed adaptor protein localized at plasma membrane-actin junctions, is essential for transmission of survival signals. Cells that are depleted of CH-ILKBP undergo extensive apoptosis despite the presence of cell–extracellular matrix contacts and soluble growth factors. The activating phosphorylation of protein kinase B (PKB/Akt), a key regulator of apoptosis, is impaired in the absence of CH-ILKBP. Importantly, loss of CH-ILKBP prevents the membrane translocation of PKB/Akt. Furthermore, forced membrane targeting of PKB/Akt bypasses the requirement of CH-ILKBP for the activating phosphorylation of PKB/Akt, suggesting that CH-ILKBP is required for the membrane translocation but not the subsequent phosphorylation of PKB/Akt. Finally, we show that loss of CH-ILKBP is also required for the full activation of extracellular signal–regulated kinase (ERK)1/2. However, restoration of the PKB/Akt activation is sufficient for protection of cells from apoptosis induced by the depletion of CH-ILKBP despite the persistent suppression of the ERK1/2 activation. Thus, CH-ILKBP is an important component of the prosurvival signaling pathway functioning primarily by facilitating the membrane translocation of PKB/Akt and consequently the activation of PKB/Akt in response to extracellular survival signals. The Rockefeller University Press 2003-03-31 /pmc/articles/PMC2172761/ /pubmed/12654898 http://dx.doi.org/10.1083/jcb.200212113 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Fukuda, Tomohiko
Guo, Lida
Shi, Xiaohua
Wu, Chuanyue
spellingShingle Fukuda, Tomohiko
Guo, Lida
Shi, Xiaohua
Wu, Chuanyue
CH-ILKBP regulates cell survival by facilitating the membrane translocation of protein kinase B/Akt
author_facet Fukuda, Tomohiko
Guo, Lida
Shi, Xiaohua
Wu, Chuanyue
author_sort Fukuda, Tomohiko
title CH-ILKBP regulates cell survival by facilitating the membrane translocation of protein kinase B/Akt
title_short CH-ILKBP regulates cell survival by facilitating the membrane translocation of protein kinase B/Akt
title_full CH-ILKBP regulates cell survival by facilitating the membrane translocation of protein kinase B/Akt
title_fullStr CH-ILKBP regulates cell survival by facilitating the membrane translocation of protein kinase B/Akt
title_full_unstemmed CH-ILKBP regulates cell survival by facilitating the membrane translocation of protein kinase B/Akt
title_sort ch-ilkbp regulates cell survival by facilitating the membrane translocation of protein kinase b/akt
description Cell survival depends on proper propagation of protective signals through intracellular signaling intermediates. We report here that calponin homology domain–containing integrin-linked kinase (ILK)–binding protein (CH-ILKBP), a widely expressed adaptor protein localized at plasma membrane-actin junctions, is essential for transmission of survival signals. Cells that are depleted of CH-ILKBP undergo extensive apoptosis despite the presence of cell–extracellular matrix contacts and soluble growth factors. The activating phosphorylation of protein kinase B (PKB/Akt), a key regulator of apoptosis, is impaired in the absence of CH-ILKBP. Importantly, loss of CH-ILKBP prevents the membrane translocation of PKB/Akt. Furthermore, forced membrane targeting of PKB/Akt bypasses the requirement of CH-ILKBP for the activating phosphorylation of PKB/Akt, suggesting that CH-ILKBP is required for the membrane translocation but not the subsequent phosphorylation of PKB/Akt. Finally, we show that loss of CH-ILKBP is also required for the full activation of extracellular signal–regulated kinase (ERK)1/2. However, restoration of the PKB/Akt activation is sufficient for protection of cells from apoptosis induced by the depletion of CH-ILKBP despite the persistent suppression of the ERK1/2 activation. Thus, CH-ILKBP is an important component of the prosurvival signaling pathway functioning primarily by facilitating the membrane translocation of PKB/Akt and consequently the activation of PKB/Akt in response to extracellular survival signals.
publisher The Rockefeller University Press
publishDate 2003
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172761/
_version_ 1611425041629577216

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