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CK2 Function in the Regulation of Akt Pathway

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Protein Kinase CK2 Cellular Function in Normal and Disease States

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 12))

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Abstract

CK2 and Akt (also known as PKB) are two antiapoptotic protein kinases, which phosphorylate hundreds of substrates. While CK2 is constitutively active, Akt, under physiological conditions, is activated by external growth/proliferation signals. However, in cancer, on the one hand, the mechanism of Akt activation is frequently dysregulated and, on the other, CK2 is usually overexpressed. Both kinases are therefore involved in tumorigenesis and considered promising drug targets.

CK2 profoundly intersects the Akt signaling: it phosphorylates several components of the Akt pathway, producing positive effects on stimulatory elements while blocking the inhibitory ones. The final outcome is that CK2 potentiates the Akt survival message.

Here we summarize the major contact points between the two kinases, focusing on the direct connection due to the CK2-dependent phosphorylation of Akt1 Ser129, but also on different levels of integration, spanning from the Akt activation mechanism at plasma membrane to the downstream effectors. It will be also highlighted how this orchestrated circuitry involving Akt and CK2 is aberrantly amplified under certain pathological circumstances, offering sites for therapeutic intervention. However, we will also review recent findings concerning specific regulation of different Akt isoforms by CK2, which can explain some of their divergent functions and warn against a too cursory pharmacological targeting of CK2/Akt, which instead can be planned only once a comprehensive picture of their connections in a specific tumor cell type has been depicted.

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Abbreviations

AML:

Acute myeloid leukemia

B-ALL:

B-cell acute lymphoblastic leukemia

CLL:

Chronic lymphocytic leukemia

CML:

Chronic myeloid leukemia

Fbxo9:

F-box only protein 9

GF:

Growth factor

NEP:

Neprilysin

PAF:

Platelet-activating factor

PD-1:

Receptor programmed death 1

PH:

Pleckstrin homology

PHLPP:

Pleckstrin homology domain leucine-rich repeat protein phosphatase

PI3K:

Phosphoinositide 3-kinase

PIP3 :

Phosphatidylinositol-3,4,5-trisphosphate

Plk3:

Polo-like kinase 3

PML:

Promyelocytic leukemia gene

PP2A:

Protein phosphatase 2A

T-ALL:

T-cell acute lymphoblastic leukemia

Tel2:

Telomere maintenance 2

TIF-1A:

Transcription initiation factor I

Tti1:

Tel2-interacting protein 1

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Padova, Via U. Bassi 58/b, Padova, 35131, Italy

    Cristina Girardi & Maria Ruzzene

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  1. Cristina Girardi
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  2. Maria Ruzzene
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Correspondence to Maria Ruzzene .

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Editors and Affiliations

  1. Department of Laboratory Medicine and Pathology, University of Minnesota Medical School and Minneapolis VA Health Care System, Minneapolis, Minnesota, USA

    Khalil Ahmed

  2. Dept of Biochemistry & Molecular Biology, University of Southern Denmark, Odense, Denmark

    Olaf-Georg Issinger

  3. Department of Molecular Biology, The John Paul II Catholic U. of Lublin Institute of Biotechnology, Lublin, Poland

    Ryszard Szyszka

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Girardi, C., Ruzzene, M. (2015). CK2 Function in the Regulation of Akt Pathway. In: Ahmed, K., Issinger, OG., Szyszka, R. (eds) Protein Kinase CK2 Cellular Function in Normal and Disease States. Advances in Biochemistry in Health and Disease, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-319-14544-0_8

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