Order or chaos? An evaluation of the regulation of protein kinase CK2

2004 ◽  
Vol 82 (6) ◽  
pp. 681-693 ◽  
Author(s):  
Mary Ellen K Olsten ◽  
David W Litchfield
Keyword(s):  
Protein Kinase ◽  
Protein Interactions ◽  
Protein Kinase Ck2 ◽  
Local Population ◽  
Protein Protein Interactions ◽  
Serine Threonine Kinase ◽  
Cellular Processes ◽  
Cellular Compartments ◽  
Cellular Components ◽  
Kinase Ck2

CK2 is a highly conserved, ubiquitously expressed protein serine/threonine kinase present in all eukaryotes. Circumscribed as having a vast array of substrates located in a number of cellular compartments, CK2 has been implicated in critical cellular processes such as proliferation, apoptosis, differentiation, and transformation. Despite advances in elucidating its substrates and involvement in cellular regulation, its precise mode of regulation remains poorly defined. In this respect, there are currently conflicting views as to whether CK2 is constitutively active or modulated in response to specific stimuli. Perhaps an important consideration in resolving these apparent discrepancies is recognition of the existence of many discrete CK2 subpopulations that are distinguished from one another by localization or association with distinct cellular components. The existence of these subpopulations brings to light the possibility of each population being regulated independently rather than the entire cellular CK2 content being regulated globally. Logically, each local population may then be regulated in a distinct manner to carry out its precise function(s). This review will examine those mechanisms including regulated expression and assembly of CK2 subunits, phosphorylation of CK2, and interactions with small molecules or cellular proteins that could contribute to the local regulation of distinct CK2 populations.Key words: protein kinase CK2, regulation, phosphorylation, protein-protein interactions, HIKE domains, regulatory interactions, CKIP-1, signal transduction.

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.

scholarly journals Systematic identification of signal integration by protein kinase A

2015 ◽  
Vol 112 (14) ◽  
pp. 4501-4506 ◽  
Author(s):  
Marie Filteau ◽  
Guillaume Diss ◽  
Francisco Torres-Quiroz ◽  
Alexandre K. Dubé ◽  
Andrea Schraffl ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Interactions ◽  
Carbon Sources ◽  
Biological Processes ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
Protein Complex Formation ◽  
Growth And Aging ◽  
Kinase A

Cellular processes and homeostasis control in eukaryotic cells is achieved by the action of regulatory proteins such as protein kinase A (PKA). Although the outbound signals from PKA directed to processes such as metabolism, growth, and aging have been well charted, what regulates this conserved regulator remains to be systematically identified to understand how it coordinates biological processes. Using a yeast PKA reporter assay, we identified genes that influence PKA activity by measuring protein–protein interactions between the regulatory and the two catalytic subunits of the PKA complex in 3,726 yeast genetic-deletion backgrounds grown on two carbon sources. Overall, nearly 500 genes were found to be connected directly or indirectly to PKA regulation, including 80 core regulators, denoting a wide diversity of signals regulating PKA, within and beyond the described upstream linear pathways. PKA regulators span multiple processes, including the antagonistic autophagy and methionine biosynthesis pathways. Our results converge toward mechanisms of PKA posttranslational regulation by lysine acetylation, which is conserved between yeast and humans and that, we show, regulates protein complex formation in mammals and carbohydrate storage and aging in yeast. Taken together, these results show that the extent of PKA input matches with its output, because this kinase receives information from upstream and downstream processes, and highlight how biological processes are interconnected and coordinated by PKA.

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 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 Different properties of four molecular forms of protein kinase CK2 from Saccharomyces cerevisiae.

2005 ◽  
Vol 52 (4) ◽  
pp. 947-952 ◽  
Author(s):  
Katarzyna Domańska ◽  
Rafał Zieliński ◽  
Konrad Kubiński ◽  
Ewa Sajnaga ◽  
Maciej Masłyk ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Molecular Forms ◽  
Beta Subunits ◽  
Wild Type ◽  
Cellular Processes ◽  
Specificity And Sensitivity ◽  
Single Deletion ◽  
Kinase Ck2 ◽  
Wild Type Yeast

CK2 is a pleiotropic constitutively active serine/threonine protein kinase composed of two catalytic alpha- and two regulatory beta-subunits, whose regulation is still not well understood. It seems to play an essential role in regulation of many cellular processes. Four active forms of CK2, composed of alphaalpha'betabeta', alpha(2)betabeta', alpha'(2)betabeta', and a free alpha'-subunit were isolated from wild-type yeast and strains containing a single deletion of the catalytic subunit. Each species exhibits properties typical for CK2, but they differ in substrate specificity and sensitivity to inhibitors. This suggests that each CK2 isomer may regulate different process or may differ in the way of its regulation.

scholarly journals High-resolution crystal structure of cAMP-dependent protein kinase fromCricetulus griseus

2015 ◽  
Vol 71 (8) ◽  
pp. 1088-1093 ◽  
Author(s):  
Denis Kudlinzki ◽  
Verena L. Linhard ◽  
Krishna Saxena ◽  
Sridhar Sreeramulu ◽  
Santosh Gande ◽  
...  
Keyword(s):  
Protein Kinase ◽  
High Resolution ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Dependent Protein Kinase ◽  
Cellular Processes ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Functional Regulation ◽  
Very High

Protein kinases (PKs) are dynamic regulators of numerous cellular processes. Their phosphorylation activity is determined by the conserved kinase core structure, which is maintained by the interaction and dynamics with associated domains or interacting proteins. The prototype enzyme for investigations to understand the activity and regulation of PKs is the catalytic subunit of cAMP-dependent protein kinase (PKAc). Major effects of functional regulation and ligand binding are driven by only minor structural modulations in protein–protein interactions. In order to resolve such minor structural differences, very high resolution structures are required. Here, the high-resolution X-ray structure of PKAc fromCricetulus griseusis reported.

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