Cell rounding in cultured human astrocytes and vascular endothelial cells upon inhibition of CK2 is mediated by actomyosin cytoskeleton alterations

Abstract

Protein kinase CK2 participates in a wide range of cellular events, including the regulation of cellular morphology and migration, and may be an important mediator of angiogenesis. We previously showed that in the retina, CK2 immunolocalizes mostly to vascular endothelium and astrocytes in association with the cytoskeleton. Additionally, CK2 inhibitors significantly reduced retinal neovascularization and stem cell recruitment in the mouse model of oxygen-induced proliferative retinopathy. We have also shown that CK2 and F-actin co-localized in actin stress fibers in microvascular endothelial cells, and that highly specific CK2 inhibitors caused cell rounding in astrocytes and microvascular endothelial cells, which was alleviated by serum that promotes spreading by Rho/Rho-kinase (RhoK) activation of myosin II. Therefore, we examined a possible role of CK2 in the regulation of actin–myosin II-based contractility. Treatment with CK2 inhibitors correlated with disassembly of actomyosin stress fibers and cell shape changes, including cytoplasmic retraction and process formation that were similar to those occurring during astrocyte stellation. Low doses of specific inhibitors of kinases (RhoK and MLCK) that phosphorylate myosin light chain (MLC) enhanced the effect of suboptimal CK2 inhibition on cell shape. Such striking stellation-like alteration was accompanied by decreased level of phospho-MLC, thus implying a CK2 role in regulation of actomyosin cytoskeleton. Our results suggest an important role of CK2 in the control of cell contractility and motility, which may account for suppressing effect of CK2 inhibition on retinal neovascularization. Together, our data implicate protein kinase CK2 for the first time in stellation-like morphological transformation.

Abemaciclib, A Selective CDK4/6 Inhibitor, Restricts the Growth of Pediatric Ependymomas

“…A previous study showed that knockdown of CK2 expression combined with neocarzinostatin treatment induced higher γH2AX expression [40]. Furthermore, another study found that inhibition of CK2 caused cytoplasmic retraction and cell rounding in cells [41][42][43]. In this study, we showed that abemaciclib treatment is associated with γH2AX expression and cytoplasmic retraction, and silmitasertib treatment also resulted in similar phenomena; therefore, we think that one possible mechanism through which abemaciclib causes cell death is through targeting of CK2.…”

Increased occurrence of protein kinase CK2 in astrocytes in Alzheimer’s disease pathology

“…Initial studies reported that CK2 is expressed in neurons [ 56 , 57 ]. More recently, Kramerov et al showed that CK2 is expressed in astroglial cells of normal and neovascularized retina, thereby suggesting that CK2 might be useful as a new immunohistochemical marker for astrocytes [ 69 , 70 ].…”

Verteporfin treatment controls morphology, phenotype, and global gene expression for cells of the human nucleus pulposus

“…While the expression profiles of the genes GNA13, BAMBI, PLEKHO1, SEMA4D, and EPB41 vary, the proteins for all five of these genes are implicated in intracellular pathways (eg, Wnt, TGF-β, PI3K-AKT, and Hippo) as well as cellular functions including control of cell shape, cell migration, response to hypoxia, regulation of cell viability, differentiation and production of ECM proteins. [101][102][103][104][105][106][107][108][109][110] functioning of membrane proteins and cell adhesion molecules. [114][115][116] Differences observed in expression of these genes are illustrative of the complex regulation used by cells to sense and respond to their mechanical and biochemical environment.…”