Angiogenin-induced protein kinase B/Akt activation is necessary for angiogenesis but is independent of nuclear translocation of angiogenin in HUVE cells

2007 ◽  
Vol 352 (2) ◽  
pp. 509-513 ◽  
Author(s):  
Hye-Mi Kim ◽  
Dong-Ku Kang ◽  
Hak Yong Kim ◽  
Sang Sun Kang ◽  
Soo-Ik Chang
Keyword(s):  
Protein Kinase ◽  
Nuclear Translocation ◽  
Protein Kinase B ◽  
Akt Activation

scholarly journals Preferential Dependence of Breast Cancer Cells versus Normal Cells on Integrin-Linked Kinase for Protein Kinase B/Akt Activation and Cell Survival

2006 ◽  
Vol 66 (1) ◽  
pp. 393-403 ◽  
Author(s):  
Armelle A. Troussard ◽  
Paul C. McDonald ◽  
Elizabeth D. Wederell ◽  
Nasrin M. Mawji ◽  
Nolan R. Filipenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Kinase ◽  
Cell Survival ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Protein Kinase B ◽  
Normal Cells ◽  
Akt Activation ◽  
Integrin Linked Kinase

scholarly journals Dual Phosphorylation of Btk by Akt/Protein Kinase B Provides Docking for 14-3-3ζ, Regulates Shuttling, and Attenuates both Tonic and Induced Signaling in B Cells

2013 ◽  
Vol 33 (16) ◽  
pp. 3214-3226 ◽  
Author(s):  
Dara K. Mohammad ◽  
Beston F. Nore ◽  
Alamdar Hussain ◽  
Manuela O. Gustafsson ◽  
Abdalla J. Mohamed ◽  
...  
Keyword(s):  
Protein Kinase ◽  
B Cell ◽  
Tyrosine Phosphorylation ◽  
Nuclear Translocation ◽  
Kinase Inhibitor ◽  
Protein Kinase B ◽  
Negative Regulator ◽  
Pleckstrin Homology Domain ◽  
Loss Of Function ◽  
Interaction Sites

Bruton's tyrosine kinase (Btk) is crucial for B-lymphocyte activation and development. Mutations in theBtkgene cause X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. Using tandem mass spectrometry, 14-3-3ζ was identified as a new binding partner and negative regulator of Btk in both B-cell lines and primary B lymphocytes. The activated serine/threonine kinase Akt/protein kinase B (PKB) phosphorylated Btk on two sites prior to 14-3-3ζ binding. The interaction sites were mapped to phosphoserine pS51 in the pleckstrin homology domain and phosphothreonine pT495 in the kinase domain. The double-alanine, S51A/T495A, replacement mutant failed to bind 14-3-3ζ, while phosphomimetic aspartate substitutions, S51D/T495D, caused enhanced interaction. The phosphatidylinositol 3-kinase (PI3-kinase) inhibitor LY294002 abrogated S51/T495 phosphorylation and binding. A newly characterized 14-3-3 inhibitor, BV02, reduced binding, as did the Btk inhibitor PCI-32765 (ibrutinib). Interestingly, in the presence of BV02, phosphorylation of Btk, phospholipase Cγ2, and NF-κB increased strongly, suggesting that 14-3-3 also regulates B-cell receptor (BCR)-mediated tonic signaling. Furthermore, downregulation of 14-3-3ζ elevated nuclear translocation of Btk. The loss-of-function mutant S51A/T495A showed reduced tyrosine phosphorylation and ubiquitination. Conversely, the gain-of-function mutant S51D/T495D exhibited intense tyrosine phosphorylation, associated with Btk ubiquitination and degradation, likely contributing to the termination of BCR signaling. Collectively, this suggests that Btk could become an important new candidate for the general study of 14-3-3-mediated regulation.

scholarly journals Chronic Protein Kinase B (PKB/c-akt) Activation Leads to Apoptosis Induced by Oxidative Stress–Mediated Foxo3a Transcriptional Up-regulation

2006 ◽  
Vol 66 (22) ◽  
pp. 10760-10769 ◽  
Author(s):  
Ankie G.M. van Gorp ◽  
Karen M. Pomeranz ◽  
Kim U. Birkenkamp ◽  
Rosaline C-Y. Hui ◽  
Eric W-F. Lam ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Protein Kinase B ◽  
Akt Activation

scholarly journals Heparanase Induces Endothelial Cell Migration via Protein Kinase B/Akt Activation

2004 ◽  
Vol 279 (22) ◽  
pp. 23536-23541 ◽  
Author(s):  
Svetlana Gingis-Velitski ◽  
Anna Zetser ◽  
Moshe Y. Flugelman ◽  
Israel Vlodavsky ◽  
Neta Ilan
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Protein Kinase ◽  
Protein Kinase B ◽  
Endothelial Cell Migration ◽  
Akt Activation

scholarly journals Hantaan virus replication is promoted via AKT activated mitochondria OXPHOS

2022 ◽  
Author(s):  
Yuhang Dong ◽  
Xiaoxiao Zhang ◽  
Mengyang Li ◽  
Qikang Ying ◽  
Yunan Feng ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Oxidative Phosphorylation ◽  
Virus Replication ◽  
Protein Kinase B ◽  
Host Cells ◽  
Hantaan Virus ◽  
Polynucleotide Phosphorylase ◽  
Major Function ◽  
Akt Activation ◽  
Intracellular Activities

Oxidative phosphorylation (OXPHOS) is a vital pathway provides ATP for intracellular activities. Here, we found that Hantaan virus (HTNV) exploited mitochondria OXPHOS to assist its replication in host cells and Protein Kinase B/AKT played a major function in this process. Inhibiting AKT activation by BEZ treatment can inhibit HTNV replication and prevent the increase of OXPHOS level caused by HTNV infection. We also found that HTNV infection can promote AKT translocation to mitochondria, where AKT phosphorylates Polynucleotide phosphorylase (PNPT). Taken together, our research demonstrates that HTNV replication exploits OXPHOS in host cells and it increases OXPHOS function by AKT-PNPT interaction in mitochondria.

Higenamine Induces Glioma Cell Death by Modulating Nuclear Factor-κB Nuclear Translocation, Phosphoinositide-3-Kinase/Protein Kinase B Signaling and Caspase Cascade

2020 ◽  
Vol 19 (3) ◽  
pp. 317-325
Author(s):  
Chao Geng ◽  
Shaowu Ou
Keyword(s):  
Protein Kinase ◽  
Nuclear Translocation ◽  
Protein Kinase B ◽  
Glioma Cells ◽  
B Cell Lymphoma ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
Nuclear Factor ◽  
Aspartic Proteases ◽  
Phosphoinositide 3 Kinase

We have investigated the effectiveness of higenamine in the treatment of malignant glioma, and explored its possible mechanism in C6 glioma cells. The efficacy of higenamine on viability of cells, apoptosis, cell cycle arrest, DNA fragmentation, and biochemical markers was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, enzyme-linked immunosorbent assay, and Western blotting. The biochemical markers investigated included the effect of higenamine on the expression of phosphoinositide-3-kinase/protein kinase B, B-cell lymphoma 2, BCL2- associated X protein, cysteine-aspartic proteases-3 and -9 proteins. The translocation of nuclear factor-kappa B from the nucleus was also analyzed. Results revealed that higenamine induced cytotoxic and antiproliferative effects on the C6 glioma cells. Higenamine led to cell arrest at G2/M phase of cell cycle and lowered cell count at S-phase. The maximum extent of DNA fragmentation was observed after 72 h exposure of higenamine. Nuclear translocation of nuclear factorkappa B was attenuated after higenamine treatment in the C6 glioma cells. The results also revealed that higenamine significantly modulated the phosphoinositide-3-kinase/protein kinase B signaling cascade. Also, higenamine elevated the cysteine-aspartic proteases-3 and -9 and BCL2-associated X protein, and downregulated B-cell lymphoma 2 expression in the C6 glioma cells. Overall, the investigation suggests higenamine modulation of phosphoinositide-3-kinase/protein kinase B signaling pathway, nuclear factor-kappa B nuclear translocation, and caspase cascade in the C6 glioma cells.

scholarly journals Protein kinase B/Akt modulates nephrotoxicant-induced necrosis in renal cells

2007 ◽  
Vol 292 (1) ◽  
pp. F292-F303 ◽  
Author(s):  
Zabeena P. Shaik ◽  
E. Kim Fifer ◽  
Grażyna Nowak
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Protein Kinase B ◽  
Primary Cultures ◽  
Protective Role ◽  
Dominant Negative ◽  
Protective Effects ◽  
Atp Content ◽  
Akt Activation ◽  
Atp Levels

Protein kinase B (Akt) activation is well known for its protective effects against apoptosis. However, the role of Akt in regulation of necrosis is unknown. This study was designed to test whether Akt activation protects against nephrotoxicant-induced injury and death in renal proximal tubular cells (RPTC). Exposure of primary cultures of RPTC to the nephrotoxic cysteine conjugate, S-(1,2-dichlorovinyl)-l-cysteine (DCVC), resulted in 9% apoptosis and 30% necrosis at 24 h following the exposure. Akt was activated during 8 h but not at 24 h following toxicant exposure. No RPTC necrosis was observed during Akt activation. Blocking Akt activation using a phosphatidylinositol 3-kinase inhibitor, LY294002 (20 μM), or expressing dominant negative (inactive) Akt increased DCVC-induced RPTC necrosis to 42%. In contrast, Akt activation by expression of constitutively active Akt diminished necrosis to 15%. Modulation of Akt activity had no effect on DCVC-induced apoptosis. DCVC-induced RPTC injury was accompanied by decreases in respiration (51% of controls) and ATP levels (57% of controls). Akt inhibition exacerbated decreases in RPTC respiration and intracellular ATP content (both to 30% of controls). In contrast, Akt activation reduced DCVC-induced decreases in respiration (80% of controls) and prevented decline in ATP content. These data show that in RPTC, Akt activation reduces 1) toxicant-induced mitochondrial dysfunction, 2) decreases in ATP levels, and 3) necrosis. We conclude that Akt activation plays a protective role against necrosis caused by nephrotoxic insult in RPTC. Furthermore, we identified mitochondria as a subcellular target of protective actions of Akt against necrosis.

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