Protein kinase CK2 is altered in insulin‐resistant genetically obese (<i>fa/fa</i>) rats

Roher, Nerea; Miró, Francesc; José, Marta; Trujillo, R.; Plana, Maria; Itarte, Emilio

doi:10.1016/s0014-5793(98)01230-7

Cited by 4 publications

(2 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, the analysis of liver tissue of insulin‐resistant obese rats (fa/fa model) and lean rats highlighted a change in CK2 distribution between the cytosol and the membranous fractions, with decreases in the cytosol and increases in the membranes of fa/fa rats compared to control rats. 264 Similarly, we found that CK2 activity and protein level were upregulated in the adipose tissue (AT) of obese and obese T2DM mice compared to their relative controls. 265 Moreover, the analysis of AT from different obese human subjects highlighted that CK2 was higher in samples from patients than from normal-weight controls, independently of their insulin resistance severity or the presence of T2DM.…”

Section: Ck2 In Human Diseasesmentioning

confidence: 75%

Protein kinase CK2: a potential therapeutic target for diverse human diseases

Borgo

D’Amore

Sarno

et al. 2021

Sig Transduct Target Ther

220

180

View full text Add to dashboard Cite

CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (either viral and host proteins). CK2 is also considered an emerging target for neurological diseases, inflammation and autoimmune disorders, diverse ophthalmic pathologies, diabetes, and obesity. In addition, CK2 activity has been associated with cardiovascular diseases, as cardiac ischemia–reperfusion injury, atherosclerosis, and cardiac hypertrophy. The hypothesis of considering CK2 inhibition for cystic fibrosis therapies has been also entertained for many years. Moreover, psychiatric disorders and syndromes due to CK2 mutations have been recently identified. On these bases, CK2 is emerging as an increasingly attractive target in various fields of human medicine, with the advantage that several very specific and effective inhibitors are already available. Here, we review the literature on CK2 implication in different human pathologies and evaluate its potential as a pharmacological target in the light of the most recent findings.

show abstract

Section: Ck2 In Human Diseasesmentioning

confidence: 75%

Protein kinase CK2: a potential therapeutic target for diverse human diseases

Borgo

D’Amore

Sarno

et al. 2021

Sig Transduct Target Ther

220

180

View full text Add to dashboard Cite

show abstract

“…In addition, CK2 has also been implicated in insulin signaling. Levels of cytosolic CK2 were increased upon insulin injection [53], and found to be reduced in insulin resistant rats [54].…”

Section: Discussionmentioning

confidence: 94%

Casein Kinase 2 Dependent Phosphorylation of Neprilysin Regulates Receptor Tyrosine Kinase Signaling to Akt

et al. 2010

View full text Add to dashboard Cite

Neprilysin (NEP) is a type II membrane metalloproteinase that cleaves physiologically active peptides at the cell surface thus regulating the local concentration of these peptides available for receptor binding and signal transduction. In addition, the cytoplasmic N-terminal domain of NEP interacts with the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) thereby regulating intracellular signaling via Akt. Thus, NEP serves dual functions in extracellular and intracellular signal transduction. Here, we show that NEP undergoes phosphorylation at serine residue 6 within the N-terminal cytoplasmic domain. In vitro and cell culture experiments demonstrate that Ser 6 is efficiently phosphorylated by protein kinase CK2. The phosphorylation of the cytoplasmic domain of NEP inhibits its interaction with PTEN. Interestingly, expression of a pseudophosphorylated NEP variant (Ser6Asp) abrogates the inhibitory effect of NEP on insulin/insulin-like growth factor-1 (IGF-1) stimulated activation of Akt. Thus, our data demonstrate a regulatory role of CK2 in the interaction of NEP with PTEN and insulin/IGF-1 signaling.

show abstract

CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity

Borgo

Milan

Favaretto

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Insulin plays a major role in glucose metabolism and insulin-signaling defects are present in obesity and diabetes. CK2 is a pleiotropic protein kinase implicated in fundamental cellular pathways and abnormally elevated in tumors. Here we report that in human and murine adipocytes CK2-inhibition decreases the insulin-induced glucose-uptake by counteracting Akt-signaling and GLUT4-translocation to the plasma membrane. In mice CK2 acts on insulin-signaling in adipose tissue, liver and skeletal muscle and its acute inhibition impairs glucose tolerance. Notably, CK2 protein-level and activity are greatly up-regulated in white adipose tissue from ob/ob and db/db mice as well as from obese patients, regardless the severity of their insulin-resistance and the presence of pre-diabetes or overt type 2 diabetes. Weight loss obtained by both bariatric surgery or hypocaloric diet reverts CK2 hyper-activation to normal level. Our data suggest a central role of CK2 in insulin-sensitivity, glucose homeostasis and adipose tissue remodeling. CK2 up-regulation is identified as a hallmark of adipose tissue pathological expansion, suggesting a new potential therapeutic target for human obesity.

show abstract

Protein kinase CK2 is altered in insulin‐resistant genetically obese (fa/fa) rats

Cited by 4 publications

References 34 publications

Protein kinase CK2: a potential therapeutic target for diverse human diseases

Protein kinase CK2: a potential therapeutic target for diverse human diseases

Casein Kinase 2 Dependent Phosphorylation of Neprilysin Regulates Receptor Tyrosine Kinase Signaling to Akt

CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity

Contact Info

Product

Resources

About