NDLI: PTEN-inhibition by zinc ions augments interleukin-2-mediated Akt phosphorylation

Please wait, while we are loading the content...

Correlations in distribution and concentration of calcium, copper and iron with zinc in isolated extracellular deposits associated with age-related macular degeneration

Zinc ions modulate protein tyrosine phosphatase 1B activity

KRAS NF-κB is involved in the development of zinc resistance and reduced curability in prostate cancer

Identification of major zinc-binding proteins from a marine cyanobacterium: insight into metal uptake in oligotrophic environments

Functional consequences of the over-expression of TRPC6 channels in HEK cells: impact on the homeostasis of zinc

PTEN-inhibition by zinc ions augments interleukin-2-mediated Akt phosphorylation

Differential impact of zinc deficiency on phagocytosis, oxidative burst, and production of pro-inflammatory cytokines by human monocytes

Affinity of zinc and copper ions for insulin monomers

Back cover

Metallomics Vol - 6 Issue - 6

Metallomics Vol - 6 Issue - 5

Metallomics Vol - 6 Issue - 4

Metallomics Vol - 6 Issue - 3

Metallomics Vol - 6 Issue - 2

PTEN-inhibition by zinc ions augments interleukin-2-mediated Akt phosphorylation

Content Provider	Royal Society of Chemistry (RSC)
Author	Plum, Laura Marie Brieger, Anne Haase, Hajo Nessel, Andreas Schwaneberg, Ulrich Rink, Lothar Engelhardt, Gabriela Hebel, Silke Arlt, Marcus Huber, Michael Kaltenberg, Jennifer
Copyright Year	2014
Abstract	Free zinc ions (Zn2+) participate in several signaling pathways. The aim of the present study was to investigate a potential involvement of Zn2+ in the PI3K/Akt pathway of interleukin (IL)-2 signaling in T-cells. The IL-2 receptor triggers three major pathways, ERK1/2, JAK/STAT5, and PI3K/Akt. We have previously shown that an IL-2-mediated release of lysosomal Zn2+ into the cytoplasm activates ERK1/2, but not STAT5. In the present study, Akt phosphorylation in response to IL-2 was abrogated by the Zn2+ chelator N,N,N′,N′-tetrakis-2(pyridyl-methyl)ethylenediamine, and was induced by treatment with Zn2+ and the ionophore pyrithione. The latter were ineffective in cells that were treated with siRNA against the phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a phosphatase that degrades the lipid second messenger PI(3,4,5)P3, which is produced by PI3K and leads to activation of Akt. Inhibition of recombinant PTEN by Zn2+in vitro yielded an IC50 of 0.59 nM. Considering a resting free cytoplasmic Zn2+ level of 0.2 nM in the T-cell line CTLL-2, this seems ideally suited for dynamic regulation by cellular Zn2+. Oxidation with H2O2 and supplementation with Zn2+ led to similar changes in the CD spectrum of PTEN. Moreover, Zn2+ partially prevented the oxidation of cysteines 71 and 124. Hence, we hypothesize that zinc signals affect the IL-2-dependent PI3K/Akt pathway by inhibiting the negative regulator PTEN through binding with a sub-nanomolar affinity to cysteine residues that are essential for its catalytic activity.
Starting Page	1277
Ending Page	1287
Page Count	11
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	6
Issue Number	7
Journal	Metallomics
DOI	10.1039/c3mt00197k
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Chromosome 10 (human) Mechanistic target of rapamycin Phosphorylation Cysteine Protein kinase B Hydrogen peroxide Cell surface receptor PTEN Small interfering RNA Phosphatase Phosphoinositide 3-kinase Ethylenediamine Interleukin 2 IC50 Chelation STAT5 Ionophore Prime Time Entertainment Network MAPK3 T cell Pyrithione Zinc Lipid Phosphatidylinositol (3,4,5)-trisphosphate Cytoplasm
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression

Role of phosphatidylinositol 3,4,5-trisphosphate in regulating the activity and localization of 3-phosphoinositide-dependent protein kinase-1.

Agonist-stimulated phosphatidylinositol-3,4,5-trisphosphate generation by scaffolded phosphoinositide kinases

The Pyridinyl Imidazole Inhibitor SB203580 Blocks Phosphoinositide-dependent Protein Kinase Activity, Protein Kinase B Phosphorylation, and Retinoblastoma Hyperphosphorylation in Interleukin-2-stimulated T Cells Independently of p38 Mitogen-activated Protein Kinase

Regulation of PI3K effector signalling in cancer by the phosphoinositide phosphatases.

A novel phosphatidylinositol(3,4,5)P3 pathway in fission yeast

PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway.

PTEN-inhibition by zinc ions augments interleukin-2-mediated Akt phosphorylation

Similar Documents

Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression

Role of phosphatidylinositol 3,4,5-trisphosphate in regulating the activity and localization of 3-phosphoinositide-dependent protein kinase-1.

Agonist-stimulated phosphatidylinositol-3,4,5-trisphosphate generation by scaffolded phosphoinositide kinases

The Pyridinyl Imidazole Inhibitor SB203580 Blocks Phosphoinositide-dependent Protein Kinase Activity, Protein Kinase B Phosphorylation, and Retinoblastoma Hyperphosphorylation in Interleukin-2-stimulated T Cells Independently of p38 Mitogen-activated Protein Kinase

Regulation of PI3K effector signalling in cancer by the phosphoinositide phosphatases.

A novel phosphatidylinositol(3,4,5)P3 pathway in fission yeast

PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway.

PTEN-inhibition by zinc ions augments interleukin-2-mediated Akt phosphorylation