The Enzymatic Phosphorylation of Proteins

Burnett, George H.; Kennedy, Eugene P.

doi:10.1016/s0021-9258(18)71184-8

Cited by 459 publications

(77 citation statements)

References 16 publications

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“…Background Of the 518 protein kinases identified in the human genome, some that have gained considerable attention are from the protein kinase CK2 family (CK2; formerly known as casein kinase II). CK2 was first discovered in 1954 by Burnett and Kennedy as a "mitochondrial enzyme" from rat liver extracts that utilized adenosine triphosphate (ATP) to phosphorylate purified casein [2]. With the dramatic improvement in biochemical techniques since then, we now know a lot more about CK2.…”

Section: Introductionmentioning

confidence: 99%

CK2 Regulation: Perspectives in 2021

Roffey

Litchfield

2021

Biomedicines

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The protein kinase CK2 (CK2) family encompasses a small number of acidophilic serine/threonine kinases that phosphorylate substrates involved in numerous biological processes including apoptosis, cell proliferation, and the DNA damage response. CK2 has also been implicated in many human malignancies and other disorders including Alzheimer′s and Parkinson’s diseases, and COVID-19. Interestingly, no single mechanism describes how CK2 is regulated, including activation by external proteins or domains, phosphorylation, or dimerization. Furthermore, the kinase has an elongated activation loop that locks the kinase into an active conformation, leading CK2 to be labelled a constitutively active kinase. This presents an interesting paradox that remains unanswered: how can a constitutively active kinase regulate biological processes that require careful control? Here, we highlight a selection of studies where CK2 activity is regulated at the substrate level, and discuss them based on the regulatory mechanism. Overall, this review describes numerous biological processes where CK2 activity is regulated, highlighting how a constitutively active kinase can still control numerous cellular activities. It is also evident that more research is required to fully elucidate the mechanisms that regulate CK2 and what causes aberrant CK2 signaling in disease.

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Section: Introductionmentioning

confidence: 99%

CK2 Regulation: Perspectives in 2021

Roffey

Litchfield

2021

Biomedicines

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“…Phosphorylation consists of the addition of a phosphate group to the side chain of amino acids. This PMT modifies the local electrostatic potential of proteins, induces conformational modifications, and affects the protein subcellular localization (for a review see [78], and [79,80]). Kinases, which are the enzymes that catalyze the transfer of phosphate group, have a role at multiple steps of HIV-1 viral, and the inhibition of cellular kinases interacting with HIV-1 at the nuclear level has been shown to affect the viral replication cycle [81].…”

Section: Hiv-1 Pr55 Gag Phosphorylationmentioning

confidence: 99%

Post-Translational Modifications of Retroviral HIV-1 Gag Precursors: An Overview of Their Biological Role

Bussienne

Marquet

Paillart

et al. 2021

IJMS

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Protein post-translational modifications (PTMs) play key roles in eukaryotes since they finely regulate numerous mechanisms used to diversify the protein functions and to modulate their signaling networks. Besides, these chemical modifications also take part in the viral hijacking of the host, and also contribute to the cellular response to viral infections. All domains of the human immunodeficiency virus type 1 (HIV-1) Gag precursor of 55-kDa (Pr55Gag), which is the central actor for viral RNA specific recruitment and genome packaging, are post-translationally modified. In this review, we summarize the current knowledge about HIV-1 Pr55Gag PTMs such as myristoylation, phosphorylation, ubiquitination, sumoylation, methylation, and ISGylation in order to figure out how these modifications affect the precursor functions and viral replication. Indeed, in HIV-1, PTMs regulate the precursor trafficking between cell compartments and its anchoring at the plasma membrane, where viral assembly occurs. Interestingly, PTMs also allow Pr55Gag to hijack the cell machinery to achieve viral budding as they drive recognition between viral proteins or cellular components such as the ESCRT machinery. Finally, we will describe and compare PTMs of several other retroviral Gag proteins to give a global overview of their role in the retroviral life cycle.

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“…In 1954 for the first time, an enzyme was isolated from liver tissue, which was able to phosphorylate the milk protein casein[ 109 ]. Fifteen years later, two distinct protein kinases with the ability to phosphorylate casein (at least in vitro ) were described and termed casein kinase 1 (CK1) and casein kinase 2 (CK2), meanwhile renamed protein kinases CK1 and CK2[ 110 ].…”

Section: Protein Kinase Ck1 Familymentioning

confidence: 99%

Stress-activated kinases as therapeutic targets in pancreatic cancer

Traub¹,

Roth²,

Kornmann³

et al. 2021

WJG

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Pancreatic cancer is a dismal disease with high incidence and poor survival rates. With the aim to improve overall survival of pancreatic cancer patients, new therapeutic approaches are urgently needed. Protein kinases are key regulatory players in basically all stages of development, maintaining physiologic functions but also being involved in pathogenic processes. c-Jun N-terminal kinases (JNK) and p38 kinases, representatives of the mitogen-activated protein kinases, as well as the casein kinase 1 (CK1) family of protein kinases are important mediators of adequate response to cellular stress following inflammatory and metabolic stressors, DNA damage, and others. In their physiologic roles, they are responsible for the regulation of cell cycle progression, cell proliferation and differentiation, and apoptosis. Dysregulation of the underlying pathways consequently has been identified in various cancer types, including pancreatic cancer. Pharmacological targeting of those pathways has been the field of interest for several years. While success in earlier studies was limited due to lacking specificity and off-target effects, more recent improvements in small molecule inhibitor design against stress-activated protein kinases and their use in combination therapies have shown promising in vitro results. Consequently, targeting of JNK, p38, and CK1 protein kinase family members may actually be of particular interest in the field of precision medicine in patients with highly deregulated kinase pathways related to these kinases. However, further studies are warranted, especially involving in vivo investigation and clinical trials, in order to advance inhibition of stress-activated kinases to the field of translational medicine.

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The Enzymatic Phosphorylation of Proteins

Cited by 459 publications

References 16 publications

CK2 Regulation: Perspectives in 2021

CK2 Regulation: Perspectives in 2021

Post-Translational Modifications of Retroviral HIV-1 Gag Precursors: An Overview of Their Biological Role

Stress-activated kinases as therapeutic targets in pancreatic cancer

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