Ribosomal S6 Kinase Cooperates with Casein Kinase 2 to Modulate the Drosophila Circadian Molecular Oscillator

Protein kinase C (PKC), p38 MAP kinase, and mitogen-activated protein kinase-activated kinases 2 and 3 (MAPKAPK2 and MAPKAPK3) have been implicated in ischemic preconditioning (PC) of the heart to reduce damage following a myocardial infarct. This study examined whether extracellular signal-regulated kinase (Erk) 1, p70 ribosomal S6 kinase (p70 S6K), casein kinase 2 (CK2), and other hsp27 kinases are also activated by PC, and if they are required for protection in rabbit hearts. CK2 and hsp27 kinase activities declined during global ischemia in control hearts, whereas PC with 5 min ischemia and 10 min reperfusion increased their activities during global ischemia. Resource Q chromatography resolved two distinct peaks of hsp27 phosphotransferase activities; the first peak (at 0.36 M NaCl) appeared to correspond to the 55-kDa MAPKAPK2. Erk1 activity was elevated in both control and PC hearts after post-ischemic reperfusion, but no change was observed in p70 S6K activity. Infarct size (measured by triphenyltetrazolium staining) in isolated rabbit hearts subjected to 30 min regional ischemia and 2 h reperfusion was 31.0 ± 2.6% of the risk zone in controls and was 10.3 ± 2.2% in PC hearts (p < 0.001). Neither the CK2 inhibitor 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) nor the Mek1/2 inhibitor PD98059 infused during ischemia blocked protection by PC. The activation of CK2 and Erk1 in ischemic preconditioned hearts appear to be epiphenomena and not required for the reduction of infarction from myocardial ischemia.Key words: Erk1, MAPKAPK2, PD98059, p38 MAPK.

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Statins as the Controlling Agents for Non-Hodgkin's Lymphomas via Increasing the Casein Kinase 2 Interacting Protein-1: A Hypothesis

Current Drug Discovery Technologies ◽

10.2174/1570163816666190628165200 ◽

2020 ◽

Vol 17 (5) ◽

pp. 616-618

Author(s):

Kimia Kazemi ◽

Negin Mozafari ◽

Hajar Ashrafi ◽

Pedram Rafiei ◽

Amir Azadi

Keyword(s):

Cell Proliferation ◽

Mevalonate Pathway ◽

Casein Kinase ◽

Casein Kinase 2 ◽

Interacting Protein ◽

Akt Phosphorylation ◽

Anticancer Properties ◽

Proliferation And Apoptosis ◽

Cellular Signaling Pathway ◽

Hodgkin's Lymphomas

Background: Non-Hodgkin's lymphomas (NHL), derived from B- or T-cell, consist of a heterogeneous group of malignant lymphoproliferative disorders. Knockdown of Casein kinase 2 interacting protein-1 (CKIP-1) in NHL promoted cell proliferation and inhibited apoptosis via enhancing phosphorylated Protein Kinase B (PKB or AKT) expression. Statins are the class of drugs that inhibit the ratelimiting step of the mevalonate pathway, which is essential for the biosynthesis of various compounds, including cholesterol. Also, statins have anticancer properties being mediated by different mechanisms. Methods: A search on databases like Scopus and PubMed with keywords such as statin and non- Hodgkin's lymphomas was performed and Kyoto Encyclopedia of Genes and Genomes (KEGG) website was used to evaluate and reconfirm the involved cellular signaling pathway. Results: CKIP-1 is involved in the regulation of cell proliferation and apoptosis while plays an important role in many cancers. We can hypothesize that statins may increase the expression levels of CKIP-1 which could contribute to the reductions in phospho-AKT level. Hence, they may ameliorate the NHL patients via suppressing AKT phosphorylation and increasing CKIP- expression. Conclusion: Present review confirms the positive effect of statins on NHL by increasing CKIP-1 and reducing cell proliferation, subsequently.

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Novel Anthraquinone Derivatives as Dual Inhibitors of Topoisomerase 2 and Casein Kinase 2: In Silico Studies, Synthesis and Biological Evaluation on Leukemic Cell Lines

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180423111309 ◽

2019 ◽

Vol 18 (11) ◽

pp. 1551-1562 ◽

Cited By ~ 4

Author(s):

Abbas Kabir ◽

Kalpana Tilekar ◽

Neha Upadhyay ◽

C.S. Ramaa

Keyword(s):

Cell Cycle ◽

Cell Line ◽

Cell Lines ◽

Biological Evaluation ◽

Casein Kinase ◽

Casein Kinase 2 ◽

Cell Cycle Analysis ◽

Protein Targets ◽

Topoisomerase 2 ◽

Dual Inhibitors

Background: Cancer being a complex disease, single targeting agents remain unsuccessful. This calls for “multiple targeting”, wherein a single drug is so designed that it will modulate the activity of multiple protein targets. Topoisomerase 2 (Top2) helps in removing DNA tangles and super-coiling during cellular replication, Casein Kinase 2 (CK2) is involved in the phosphorylation of a multitude of protein targets. Thus, in the present work, we have tried to develop dual inhibitors of Top2 and CK2. Objective: With this view, in the present work, 2 human proteins, Top2 and CK2 have been targeted to achieve the anti-proliferative effects. Methods: Novel 1-acetylamidoanthraquinone (3a-3y) derivatives were designed, synthesized and their structures were elucidated by analytical and spectral characterization techniques (FTIR, 1H NMR, 13C NMR and Mass Spectroscopy). The synthesized compounds were then subjected to evaluation of cytotoxic potential by the Sulforhodamine B (SRB) protein assay, using HL60 and K562 cell lines. Ten compounds were analyzed for Top2, CK2 enzyme inhibitory potential. Further, top three compounds were subjected to cell cycle analysis. Results: The compounds 3a to 3c, 3e, 3f, 3i to 3p, 3t and 3x showed excellent cytotoxic activity to HL-60 cell line indicating their high anti-proliferative potential in AML. The compounds 3a to 3c, 3e, 3f, 3i to 3p and 3y have shown good to moderate activity on K-562 cell line. Compounds 3e, 3f, 3i, 3x and 3y were found more cytotoxic than standard doxorubicin. In cell cycle analysis, the cells (79-85%) were found to arrest in the G0/G1 phase. Conclusion: We have successfully designed, synthesized, purified and structurally characterized 1- acetylamidoanthraquinone derivatives. Even though our compounds need design optimization to further increase enzyme inhibition, their overall anti-proliferative effects were found to be encouraging.

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Phosphorylation of glycogen synthase by cyclic AMP-independent casein kinase-2 from rabbit skeletal muscle.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)81101-8 ◽

1982 ◽

Vol 257 (6) ◽

pp. 3236-3242

Author(s):

K P Huang ◽

E Itarte ◽

T J Singh ◽

A Akatsuka

Keyword(s):

Skeletal Muscle ◽

Cyclic Amp ◽

Glycogen Synthase ◽

Casein Kinase ◽

Casein Kinase 2 ◽

Rabbit Skeletal Muscle

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Casein Kinase 2 dependent phosphorylation of eIF4B regulates BACE1 expression in Alzheimer’s disease

Cell Death and Disease ◽

10.1038/s41419-021-04062-3 ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Barbara Bettegazzi ◽

Laura Sebastian Monasor ◽

Serena Bellani ◽

Franca Codazzi ◽

Lisa Michelle Restelli ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neuronal Activity ◽

Neurodegenerative Disorder ◽

Brain Slices ◽

Casein Kinase ◽

Casein Kinase 2 ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Bace1 Expression

AbstractAlzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. Increased Aβ production plays a fundamental role in the pathogenesis of the disease and BACE1, the protease that triggers the amyloidogenic processing of APP, is a key protein and a pharmacological target in AD. Changes in neuronal activity have been linked to BACE1 expression and Aβ generation, but the underlying mechanisms are still unclear. We provide clear evidence for the role of Casein Kinase 2 in the control of activity-driven BACE1 expression in cultured primary neurons, organotypic brain slices, and murine AD models. More specifically, we demonstrate that neuronal activity promotes Casein Kinase 2 dependent phosphorylation of the translation initiation factor eIF4B and this, in turn, controls BACE1 expression and APP processing. Finally, we show that eIF4B expression and phosphorylation are increased in the brain of APPPS1 and APP-KI mice, as well as in AD patients. Overall, we provide a definition of a mechanism linking brain activity with amyloid production and deposition, opening new perspectives from the therapeutic standpoint.

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Aging does not alter the mechanosensitivity of the p38, p70S6k, and JNK2 signaling pathways in skeletal muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.00870.2004 ◽

2005 ◽

Vol 98 (4) ◽

pp. 1562-1566 ◽

Cited By ~ 34

Author(s):

Troy A. Hornberger ◽

R. D. Mateja ◽

E. R. Chin ◽

J. L. Andrews ◽

K. A. Esser

Keyword(s):

Skeletal Muscle ◽

Signaling Pathways ◽

Ex Vivo ◽

Mechanical Stimuli ◽

S6 Kinase ◽

Diminished Capacity ◽

Ribosomal S6 Kinase ◽

Passive Stretch ◽

Old Mice ◽

Dependent Mechanism

The capacity for skeletal muscle to recover its mass following periods of unloading (regrowth) has been reported to decline with age. Although the mechanisms responsible for the impaired regrowth are not known, it has been suggested that aged muscles have a diminished capacity to sense and subsequently respond to a given amount of mechanical stimuli (mechanosensitivity). To test this hypothesis, extensor digitorum longus muscles from young (2–3 mo) and old (26–27 mo) mice were subjected to intermittent 15% passive stretch (ex vivo) as a source of mechanical stimulation and analyzed for alterations in the phosphorylation of stress-activated protein kinase (p38), ribosomal S6 kinase (p70S6k), and the p54 jun N-terminal kinase (JNK2). The results indicated that the average magnitude of specific tension (mechanical stimuli) induced by 15% stretch was similar in muscles from young and old mice. Young and old muscles also revealed similar increases in the magnitude of mechanically induced p38, p70S6k (threonine/serine 421/424 and threonine 389), and JNK2 phosphorylation. In addition, coincubation experiments demonstrated that the release of locally acting growth factors was not sufficient for the induction of JNK2 phosphorylation, suggesting that JNK2 was activated by a mechanical rather than a mechanical/growth factor-dependent mechanism. Taken together, the results of this study demonstrate that aging does not alter the mechanosensitivity of the p38, p70S6k, and JNK2 signaling pathways in skeletal muscle.

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p90 ribosomal S6 kinase 3 contributes to cardiac insufficiency in α-tropomyosin Glu180Gly transgenic mice

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00237.2013 ◽

2013 ◽

Vol 305 (7) ◽

pp. H1010-H1019 ◽

Cited By ~ 10

Author(s):

Catherine L. Passariello ◽

Marjorie Gayanilo ◽

Michael D. Kritzer ◽

Hrishikesh Thakur ◽

Zoharit Cozacov ◽

...

Keyword(s):

Heart Failure ◽

Transgenic Mice ◽

Cardiac Function ◽

Interstitial Fibrosis ◽

Cardiac Insufficiency ◽

S6 Kinase ◽

Transgenic Expression ◽

P90 Ribosomal S6 Kinase ◽

Ribosomal S6 Kinase

Myocardial interstitial fibrosis is an important contributor to the development of heart failure. Type 3 p90 ribosomal S6 kinase (RSK3) was recently shown to be required for concentric myocyte hypertrophy under in vivo pathological conditions. However, the role of RSK family members in myocardial fibrosis remains uninvestigated. Transgenic expression of α-tropomyosin containing a Glu180Gly mutation (TM180) in mice of a mixed C57BL/6:FVB/N background induces a cardiomyopathy characterized by a small left ventricle, interstitial fibrosis, and diminished systolic and diastolic function. Using this mouse model, we now show that RSK3 is required for the induction of interstitial fibrosis in vivo. TM180 transgenic mice were crossed to RSK3 constitutive knockout ( RSK3−/−) mice. Although RSK3 knockout did not affect myocyte growth, the decreased cardiac function and mild pulmonary edema associated with the TM180 transgene were attenuated by RSK3 knockout. The improved cardiac function was consistent with reduced interstitial fibrosis in the TM180; RSK3−/− mice as shown by histology and gene expression analysis, including the decreased expression of collagens. The specific inhibition of RSK3 should be considered as a potential novel therapeutic strategy for improving cardiac function and the prevention of sudden cardiac death in diseases in which interstitial fibrosis contributes to the development of heart failure.

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