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CH-ILKBP regulates cell survival by facilitating the membrane translocation of protein kinase B/Akt
- Source :
- The Journal of Cell Biology
- Publication Year :
- 2003
- Publisher :
- Rockefeller University Press, 2003.
-
Abstract
- 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.
- Subjects :
- Cell Survival
Green Fluorescent Proteins
AKT1
Apoptosis
Protein Serine-Threonine Kinases
Biology
DEPTOR
mTORC2
03 medical and health sciences
0302 clinical medicine
Proto-Oncogene Proteins
Report
apoptosis
CH-ILKBP
protein kinase B/Akt
membrane translocation
ILK
Tumor Cells, Cultured
Humans
Actinin
Phosphorylation
RNA, Small Interfering
Protein kinase B
PI3K/AKT/mTOR pathway
030304 developmental biology
Mitogen-Activated Protein Kinase 1
0303 health sciences
Mitogen-Activated Protein Kinase 3
Akt/PKB signaling pathway
Cell Membrane
Microfilament Proteins
Biological Transport
Cell Biology
Extracellular Matrix
Cell biology
Enzyme Activation
Luminescent Proteins
Caspases
030220 oncology & carcinogenesis
Mitogen-Activated Protein Kinases
Signal transduction
Carrier Proteins
Proto-Oncogene Proteins c-akt
HeLa Cells
Protein Binding
Subjects
Details
- ISSN :
- 15408140 and 00219525
- Volume :
- 160
- Database :
- OpenAIRE
- Journal :
- Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....b2a8b6dbb307aa36967487cf9a410dca