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Differential effects of Akt pathway inhibitors on IL-1β-induced protein phosphorylation in human fibroblast-like synoviocytes
Differential effects of Akt pathway inhibitors on IL-1β-induced protein phosphorylation in human fibroblast-like synoviocytes
- Source :
- Journal of Receptors and Signal Transduction. 32:22-28
- Publication Year :
- 2011
- Publisher :
- Informa UK Limited, 2011.
-
Abstract
- Interleukin (IL)-1β activates various signal transduction pathways including p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and Akt in human fibroblast-like synoviocytes (HFLS).We investigated the effects of an Akt inhibitor, a phosphatidylinositol 3-kinase (PI3K) inhibitor, and Akt RNAi knockdown on IL-1β-induced protein phosphorylation in HFLS to clarify the role of the PI3K/Akt signaling pathway in the phosphorylation of the inhibitor of κB (IκB)α and heat shock protein 27 (HSP27).A multiplex suspension array system was used for the detection of phosphorylated proteins.IL-1β induced biphasic phosphorylation of IκBα, with the first phase occurring 10 min after IL-1β stimulation, and this was augmented by treatment with Akt inhibitor IV. However, this phenomenon was not observed after treatment with LY-294002, a PI3K inhibitor. Furthermore, Akt inhibitor IV suppressed ERK2 phosphorylation, whereas LY-294002 and Akt RNAi had no effect. In contrast, Akt inhibitor IV, LY-294002, and Akt RNAi augmented HSP27 phosphorylation.Modulation of different stages of the PI3K/Akt pathway may differentially affect the phosphorylation of IκBα and HSP27 in HFLS.
- Subjects :
- Morpholines
p38 mitogen-activated protein kinases
Interleukin-1beta
HSP27 Heat-Shock Proteins
Biochemistry
NF-KappaB Inhibitor alpha
Humans
Protein phosphorylation
Phosphorylation
Protein kinase A
Molecular Biology
Protein kinase B
Cells, Cultured
PI3K/AKT/mTOR pathway
Phosphoinositide-3 Kinase Inhibitors
Mitogen-Activated Protein Kinase 1
Akt/PKB signaling pathway
Chemistry
Synovial Membrane
Cell Biology
Fibroblasts
Molecular biology
Oncogene Protein v-akt
Chromones
Gene Knockdown Techniques
I-kappa B Proteins
RNA Interference
Phosphatidylinositol 3-Kinase
Signal transduction
Subjects
Details
- ISSN :
- 15324281 and 10799893
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Journal of Receptors and Signal Transduction
- Accession number :
- edsair.doi.dedup.....0d9b925d2682369b78227c8160fe908f
- Full Text :
- https://doi.org/10.3109/10799893.2011.641976