scholarly journals The Alpha Catalytic Subunit of Protein Kinase CK2 Is Required for Mouse Embryonic Development

2007 ◽  
Vol 28 (1) ◽  
pp. 131-139 ◽  
Author(s):  
David Y. Lou ◽  
Isabel Dominguez ◽  
Paul Toselli ◽  
Esther Landesman-Bollag ◽  
Conor O'Brien ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Embryonic Development ◽  
Protein Kinase Ck2 ◽  
Germ Line ◽  
Cell Physiology ◽  
Mammalian Development ◽  
Serine Threonine Kinase ◽  
Regulatory Subunits ◽  
Neural Tubes ◽  
Kinase Ck2

ABSTRACT Protein kinase CK2 (formerly casein kinase II) is a highly conserved and ubiquitous serine/threonine kinase that is composed of two catalytic subunits (CK2α and/or CK2α′) and two CK2β regulatory subunits. CK2 has many substrates in cells, and key roles in yeast cell physiology have been uncovered by introducing subunit mutations. Gene-targeting experiments have demonstrated that in mice, the CK2β gene is required for early embryonic development, while the CK2α′ subunit appears to be essential only for normal spermatogenesis. We have used homologous recombination to disrupt the CK2α gene in the mouse germ line. Embryos lacking CK2α have a marked reduction in CK2 activity in spite of the presence of the CK2α′ subunit. CK2α−/− embryos die in mid-gestation, with abnormalities including open neural tubes and reductions in the branchial arches. Defects in the formation of the heart lead to hydrops fetalis and are likely the cause of embryonic lethality. Thus, CK2α appears to play an essential and uncompensated role in mammalian development.

scholarly journals Protein kinase CK2: structure, regulation and role in cellular decisions of life and death

2003 ◽  
Vol 369 (1) ◽  
pp. 1-15 ◽  
Author(s):  
David W. LITCHFIELD
Keyword(s):  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Current Knowledge ◽  
Cellular Functions ◽  
Serine Threonine Kinase ◽  
Life And Death ◽  
Dual Specificity ◽  
Mechanistic Basis ◽  
Kinase Ck2

Protein kinase CK2 ('casein kinase II') has traditionally been classified as a messenger-independent protein serine/threonine kinase that is typically found in tetrameric complexes consisting of two catalytic (α and/or α′) subunits and two regulatory β subunits. Accumulated biochemical and genetic evidence indicates that CK2 has a vast array of candidate physiological targets and participates in a complex series of cellular functions, including the maintenance of cell viability. This review summarizes current knowledge of the structural and enzymic features of CK2, and discusses advances that challenge traditional views of this enzyme. For example, the recent demonstrations that individual CK2 subunits exist outside tetrameric complexes and that CK2 displays dual-specificity kinase activity raises new prospects for the precise elucidation of its regulation and cellular functions. This review also discusses a number of the mechanisms that contribute to the regulation of CK2 in cells, and will highlight emerging insights into the role of CK2 in cellular decisions of life and death. In this latter respect, recent evidence suggests that CK2 can exert an anti-apoptotic role by protecting regulatory proteins from caspase-mediated degradation. The mechanistic basis of the observation that CK2 is essential for viability may reside in part in this ability to protect cellular proteins from caspase action. Furthermore, this anti-apoptotic function of CK2 may contribute to its ability to participate in transformation and tumorigenesis.

Crystal structures of catalytic and regulatory subunits of rat protein kinase CK2

2009 ◽  
Vol 54 (2) ◽  
pp. 220-226 ◽  
Author(s):  
WeiHong Zhou ◽  
XiaoHong Qin ◽  
XiaoJie Yan ◽  
XingQiao Xie ◽  
Liang Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Crystal Structures ◽  
Protein Kinase Ck2 ◽  
Regulatory Subunits ◽  
Kinase Ck2

scholarly journals The Immune Regulatory Role of Protein Kinase CK2 and Its Implications for Treatment of Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1932
Author(s):  
Huixian Hong ◽  
Etty N. Benveniste
Keyword(s):  
T Cells ◽  
Protein Kinase ◽  
Immune Cells ◽  
Protein Kinase Ck2 ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Kinase Ck2

Protein Kinase CK2, a constitutively active serine/threonine kinase, fulfills its functions via phosphorylating hundreds of proteins in nearly all cells. It regulates a variety of cellular signaling pathways and contributes to cell survival, proliferation and inflammation. CK2 has been implicated in the pathogenesis of hematologic and solid cancers. Recent data have documented that CK2 has unique functions in both innate and adaptive immune cells. In this article, we review aspects of CK2 biology, functions of the major innate and adaptive immune cells, and how CK2 regulates the function of immune cells. Finally, we provide perspectives on how CK2 effects in immune cells, particularly T-cells, may impact the treatment of cancers via targeting CK2.

scholarly journals Protein kinase CK2 both promotes robust proliferation and inhibits the proliferative fate in the C. elegans germ line

2014 ◽  
Vol 392 (1) ◽  
pp. 26-41 ◽  
Author(s):  
Xin Wang ◽  
Pratyush Gupta ◽  
Jared Fairbanks ◽  
Dave Hansen
Keyword(s):  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Germ Line ◽  
C Elegans ◽  
Kinase Ck2

Yeast holoenzyme of protein kinase CK2 requires both β and β′ regulatory subunits for its activity

2006 ◽  
Vol 295 (1-2) ◽  
pp. 229-236 ◽  
Author(s):  
Konrad Kubiński ◽  
Katarzyna Domańska ◽  
Ewa Sajnaga ◽  
Elżbieta Mazur ◽  
Rafał Zieliński ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Regulatory Subunits ◽  
Kinase Ck2

Assembly of protein kinase CK2: investigation of complex formation between catalytic and regulatory subunits using a zinc-finger-deficient mutant of CK2β

2001 ◽  
Vol 358 (1) ◽  
pp. 87-94 ◽  
Author(s):  
David A. CANTON ◽  
Cunjie ZHANG ◽  
David W. LITCHFIELD
Keyword(s):  
Protein Kinase ◽  
Zinc Finger ◽  
Protein Kinase Ck2 ◽  
Deficient Mutant ◽  
Binding Assays ◽  
Catalytic Subunits ◽  
Regulatory Subunits ◽  
Regulatory Ck2β Subunit ◽  
Kinase Ck2

Protein kinase CK2 is a tetrameric enzyme comprised of two regulatory subunits (CK2β) and two catalytic subunits (CK2α and/or CK2α′). The crystal structure of dimeric CK2β demonstrated that a zinc finger mediates CK2β dimerization, therefore we constructed a mutant in which cysteine residues 109 and 114 were mutated to serine. Our objectives were to examine the effects of disrupting the zinc finger of the regulatory CK2β subunit on CK2 tetramer assembly. Examination of this zinc-finger-deficient mutant of CK2β using a yeast two-hybrid assay demonstrates that the mutant fails to form CK2β homodimers. In order to extend these studies, we co-transfected COS-7 cells with epitope-tagged constructs and performed co-immunoprecipitation assays. The results from these studies demonstrate that the mutant fails to form CK2β homodimers and fails to interact with catalytic CK2 subunits. Furthermore, we demonstrate that the mutant CK2β is not appreciably phosphorylated in cells. Using in vitro binding assays, we demonstrated that the mutant CK2β protein fails to interact with glutathione S-transferase–CK2α′. Finally, we demonstrate that the mutant is translated at an equivalent rate to wild-type CK2β, but is degraded much more rapidly. Overall, our results are consistent with the model that β–β dimerization precedes incorporation of catalytic subunits into tetrameric CK2 complexes, and that β–β dimerization is a prerequisite for the stable incorporation of catalytic subunits into CK2 complexes.

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