Human Protein Kinase CK2 Phosphorylates Matrix Metalloproteinase 2 and Inhibits its Activity

Filipiak, Kamila; Kubiński, Konrad; Hellman, Ulf; Ramos, Ana; Pascual‐Teresa, Beatriz de

doi:10.1002/cbic.201402036

Cited by 7 publications

(3 citation statements)

References 28 publications

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“…These effects were attributed to the sequential attenuation of proteins in the PI3K/AKT and MAPK pathways [ 344 ]. Furthermore, CK2 has been shown to phosphorylate and inhibit MMP-2 in vitro, an effect that could be abolished by the inhibition of CK2 with TBB [ 428 ].…”

Section: Importance Of Ck2 In Different Hallmarks Of Cancermentioning

confidence: 99%

CK2 and the Hallmarks of Cancer

Firnau

Brieger

2022

Biomedicines

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Cancer is a leading cause of death worldwide. Casein kinase 2 (CK2) is commonly dysregulated in cancer, impacting diverse molecular pathways. CK2 is a highly conserved serine/threonine kinase, constitutively active and ubiquitously expressed in eukaryotes. With over 500 known substrates and being estimated to be responsible for up to 10% of the human phosphoproteome, it is of significant importance. A broad spectrum of diverse types of cancer cells has been already shown to rely on disturbed CK2 levels for their survival. The hallmarks of cancer provide a rationale for understanding cancer’s common traits. They constitute the maintenance of proliferative signaling, evasion of growth suppressors, resisting cell death, enabling of replicative immortality, induction of angiogenesis, the activation of invasion and metastasis, as well as avoidance of immune destruction and dysregulation of cellular energetics. In this work, we have compiled evidence from the literature suggesting that CK2 modulates all hallmarks of cancer, thereby promoting oncogenesis and operating as a cancer driver by creating a cellular environment favorable to neoplasia.

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Section: Importance Of Ck2 In Different Hallmarks Of Cancermentioning

confidence: 99%

CK2 and the Hallmarks of Cancer

Firnau

Brieger

2022

Biomedicines

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“…There is evidence that human MMP-2 is phosphorylated on serine and threonine residues. In vitro phosphorylation of MMP-2 by protein kinase C (Sariahmetoglu et al, 2007) and protein kinase CK2 (Filipiak et al, 2014) reduces their activity. The phosphorylation of the cytoplasmic domain of MMP-14 has also been reported, although the functional consequence of this phosphorylation is unknown.…”

Section: Mmp Activationmentioning

confidence: 99%

Metalloproteinases of the extracellular matrix and their inhibitors

Kudaka

Łodej

Baier

et al. 2016

bta

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The dynamic equilibrium between the synthesis and degradation of the extracellular matrix is to a large extent mediated by matrix metalloproteinase (MMP) enzymes, which are antagonized by tissue inhibitors of metalloproteinases (TIMPs). Tissue-degrading enzymes of the metalloproteinase family have been implicated in the pathogenesis of several conditions involving the extracellular matrix. MMPs are a family of zinc-dependent endopeptidases capable of degrading practically all components of the extracellular matrix. Recent insights suggest that MMPs may also have a broader spectrum of functions, including regulation of the inflammatory response and cytokine signaling. MMPs have been subdivided according to their main degradation activity and the continuously growing list of known substrates. Metalloproteinases are promising drug targets, and they are subjected to pharmacological inhibition by clinically available drugs such as tetracyclines and bisphosphonates. Interest in MMPs has recently increased, because their expression is frequently related to tumor progression. As such, metalloproteinases have diagnostic potential as markers to predict the outcome of disease processes. This review introduces the members of the MMP family and discusses their domain structure and function, their significance in physiology and pathology and the mechanism of inhibition by TIMPs.

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“…Although, many studies reveal the vital role of CK2 in cancer cell proliferation and survival [11], and its activation is shown to inhibit the transcriptional activity of stimulatory protein-1 (SP-1) by suppressing its DNA binding activity through phosphorylation of the carboxy-terminal domain of SP-1 [12]. In addition to gene regulation, CK2 also suppresses gelatinolytic activity by phosphorylating the matrix metalloproteinase-2 (MMP-2) to inhibit cancer cell invasion [13]. The upstream promoter sequences of MMP-2 and MMP-9 contain binding sites for the transcription factors, nuclear factor kappa B (NF-κB) and SP-1 [14,15].…”

Section: Introductionmentioning

confidence: 99%

Enforced C-Src Activation Causes Compartmental Dysregulation of PI3K and PTEN Molecules in Lipid Rafts of Tongue Squamous Carcinoma Cells by Attenuating Rac1-Akt-GLUT-1-Mediated Sphingolipid Synthesis

Wang

Lee

et al. 2020

IJMS

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Pharmacologic intervention to affect the membrane lipid homeostasis of lipid rafts is a potent therapeutic strategy for cancer. Here we showed that gallic acid (GA) caused the complex formation of inactive Ras-related C3 botulinum toxin substrate 1 (Rac1)-phospho (p)-casein kinase 2 α (CK2α) (Tyr 255) in human tongue squamous carcinoma (TSC) cells, which disturbed the lipid raft membrane-targeting of phosphatidylinositol 3-kinase (PI3K)-Rac1-protein kinase B (Akt) signal molecules by inducing the association of p110α-free p85α with unphosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN) in lipid rafts. The effects on induction of inactive Rac1-p-CK2α (Tyr 255) complex formation and attenuation of p-Akt (Ser 473), GTP-Rac1, glucose transporter-1 (GLUT-1) lipid raft membrane-targeting, and cell invasive activity by GA were counteracted either by CK2α short hairpin RNA or cellular-Src (c-Src) inhibitor PP1. PP1 treatment, GLUT-1 or constitutively active Rac1 ectopic-expression blocked GA-induced decreases in cellular glucose, sphingolipid and cholesterol of lipid raft membranes, p85α-p110α-GTP-Rac1 complexes, glucosylceramide synthase activity and increase in ceramide and p110α-free p85α-PTEN complex levels of lipid raft membranes, which reversed the inhibition on matrix metalloproteinase (MMP)-2/-9-mediated cell invasion induced by GA. Using transient ectopic expression of nuclear factor-kappa B (NF-κB) p65, MMP-2/-9 promoter-driven luciferase, and NF-κB-dependent luciferase reporter genes and NF-κB specific inhibitors or Rac1 specific inhibitor NSC23766, we confirmed that an attenuation of Rac1 activity by GA confers inhibition of NF-κB-mediated MMP-2/-9 expression and cell invasion. In conclusion, GA-induced c-Src activation is a key inductive event for the formation of inactive Rac1-p-CK2α (Tyr 255) complexes, which disturbed lipid raft compartment of PI3K and PTEN molecules by impairing Akt-regulated GLUT-1-mediated sphingolipid synthesis, and finally resulting in inhibition of TSC cell invasion.

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Human Protein Kinase CK2 Phosphorylates Matrix Metalloproteinase 2 and Inhibits its Activity

Cited by 7 publications

References 28 publications

CK2 and the Hallmarks of Cancer

CK2 and the Hallmarks of Cancer

Metalloproteinases of the extracellular matrix and their inhibitors

Enforced C-Src Activation Causes Compartmental Dysregulation of PI3K and PTEN Molecules in Lipid Rafts of Tongue Squamous Carcinoma Cells by Attenuating Rac1-Akt-GLUT-1-Mediated Sphingolipid Synthesis

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