CK2α is essential for embryonic morphogenesis

Domı́nguez, Isabel; Dégano, Irene R.; Chea, Kathleen; Cha, Julie; Toselli, Paul; Seldin, David C.

doi:10.1007/s11010-011-0961-8

Cited by 36 publications

(40 citation statements)

References 52 publications

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“…The forelimb and hindlimb buds are hypoplastic in CK2α knockouts [ 18 ]; however, we did not observe an apparent difference in the epithelium or mesenchyme of the limb buds compared to wild type.…”

Section: Histological Analysis Of Ck2α Knockoutscontrasting

confidence: 80%

“…In addition, the division between the heart chambers in the CK2α knockout is not as apparent as in the wild type. The somites (precursors of body muscles and vertebra) in CK2α knockout mice at E9.5 are hypoplastic, particularly the posterior somites [ 18 ]. In addition, our histological analysis showed that the cellular organization of the somites is abnormal.…”

Section: Histological Analysis Of Ck2α Knockoutsmentioning

confidence: 78%

“…At E9.5, most of the CK2α knockout embryos only had one hypoplastic fi rst pharyngeal arch, and some failed to develop any pharyngeal arches (wild type embryos have two pharyngeal arches at this stage) [ 18 ]. By E10.5, the total number and size of the pharyngeal arches was smaller in CK2α knockouts compared to wild type embryos [ 18 ]. At both E9.5 and E10.5, the endodermal lining of the pharyngeal arches was disorganized in CK2α knockouts compared to wild type.…”

Section: Histological Analysis Of Ck2α Knockoutsmentioning

confidence: 99%

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CK2 in Organ Development, Physiology, and Homeostasis

Ortega

Prince-Wright

Domı́nguez

2015

Protein Kinase CK2 Cellular Function in Normal and Disease States

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The serine/threonine kinase CK2 is associated with a wide variety of cellular processes, including cell growth, cell proliferation, and cell apoptosis. These cellular processes are vital for proper cell function, organogenesis, embryogenesis, and organ homeostasis. Indeed, CK2 is essential for embryonic development in different model organisms; however, the cellular, biochemical, molecular, and signaling mechanisms that CK2 utilizes to control embryo development are poorly defi ned. In this chapter, we review the effect of CK2α knockout in the developing organs and review the literature to understand the role of CK2α in organ formation. Published studies show roles for CK2 in the control of embryonic organ development, as well as a role for CK2α in organ homeostasis and physiology. In addition, CK2 also plays a role in a number of organ diseases.

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Section: Histological Analysis Of Ck2α Knockoutscontrasting

confidence: 80%

Section: Histological Analysis Of Ck2α Knockoutsmentioning

confidence: 78%

Section: Histological Analysis Of Ck2α Knockoutsmentioning

confidence: 99%

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CK2 in Organ Development, Physiology, and Homeostasis

Ortega

Prince-Wright

Domı́nguez

2015

Protein Kinase CK2 Cellular Function in Normal and Disease States

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“…There is some indication that CK2 plays a role in spermatogenesis [8,7,23] as well as during certain stages of embryogenesis [24,25]. Furthermore, it was shown by several groups that CK2 seems to be an important protein kinase for a variety of different cellular processes in developing organs and organogenesis [5,6,26,27]. In the differentiation of pre-adipocytes into adipocytes, CK2 was found to be accompanied by a decrease in the protein level and in the kinase activity [28,29].…”

mentioning

confidence: 99%

Protein Kinase CK2 and Angiogenesis

Montenarh¹

2014

Adv Clin Exp Med

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CK2 is an ubiquitously expressed protein kinase, which is composed of two catalytic a-and a'-and two noncatalytic b-subunits. CK2 protein levels and kinase activity is elevated in rapidly proliferating cells including cancer cells. There is increasing evidence that CK2 also plays an essential role in angiogenesis, either by interaction or phosphorylation of growth factors or by phosphorylation or binding to proteins in signalling cascades, which are implicated in angiogenesis. Over the last ten years a great number of inhibitors for CK2 were detected, two of them are now in clinical phase II trials for the treatment of cancer patients. Some of these inhibitors were also found to be active in the inhibition of angiogenesis. Thus, CK2 inhibitors probably together with inhibitors of other signalling molecules involved in angiogenesis might be powerful tools for the treatment of cancer and cancer connected angiogenesis (Adv Clin Exp Med 2014, 23, 2, 153-158).

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“…17) It was reported to be implicated in a series of physiological and pathological processes, including various cancers, 18) bone formation, 19) mouse globozoospermia, 15) embryonic morphogenesis, 20) and chronic intestinal inammation. 21) We have previously identified CK2 as a GN-related gene and indicated that CK2 could be a therapeutic target for treating GN.…”

Section: Discussionmentioning

confidence: 99%

The Effects of a Selective CK2 Inhibitor on Anti-glomerular Basement Membrane Glomerulonephritis in Rats

Shi

Liu

Xiao

et al. 2015

Biological & Pharmaceutical Bulletin

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Protein kinase CK2 ("casein kinase II") is a protein serine/threonine kinase that plays critical roles in biological processes such as cell growth, cell cycle progression, and apoptosis. So far, we have identified that one catalytic isozyme of CK2, CK2α, is over-expressed in the kidney during the progression of glomerulonephritis (GN). Moreover, we have shown that in vivo inhibition of CK2 by administration of CK2 inhibitors was effective in the treatment of experimental GN. Hence the development of potent CK2 inhibitors should be considered in therapeutic strategies for GN. In the present study we identified compound 13, a pyrazine derivative, as a potent CK2 inhibitor. By performing enzyme kinetics analysis in vitro, we characterized the inhibition of compound 13 toward each CK2 catalytic isozyme. Furthermore, in vivo, we demonstrated that compound 13 is effective in attenuating proteinuria, decreasing the enhanced level of blood urea nitrogen and serum creatinine, and ameliorating glomerular crescent formation in an experimental GN rat model. On the other hand, cellular apoptosis was detected in the rat testis following administration of compound 13. This study provides clues for new strategies for developing applicable compounds into CK2-targeted GN treatments.Key words protein kinase CK2; glomerulonephritis (GN); CK2 inhibitor; testicular toxicity Protein kinase CK2 (formerly called "casein kinase 2") is a serine/threonine kinase ubiquitously distributed in eukaryotic organisms. CK2 phosphorylates more than 300 proteins, 1) and its roles in cells are various, including cell proliferation, cell growth, cell division, and cell apoptosis.2) The CK2 holoenzyme in mammals exists predominantly as a heterotetramer composed of two catalytic subunits (α and/or α′) and two regulatory subunits (β). The two catalytic isozymes of CK2, CK2α and CK2α′, have been well characterized. CK2α and CK2α′ exhibit approximately 90% identity in their catalytic domains, even though they arise from different chromosomes.2) Although they may display similar enzymatic properties (including turnover rates and substrate specificity) in vitro, the two isozymes may play different roles in vivo, since CK2α is widely distributed in various tissues, whereas CK2α′ is mainly expressed in the brain and testis.3) In a report, the deficiency of CK2α in mice caused embryonic lethality, while the knockout of CK2α′ in mice induced spermatocytes to undergo apoptosis and the surviving spermatozoa to exhibit abnormal morphology. 4) Hence, CK2α and CK2α′ may have distinct functions.We have previously identified CK2α, but not CK2α′, as a glomerulonephritis (GN)-related gene using cDNA microarray analysis. 5) In the same study, we observed that administration of either antisense oligodeoxynucleotide against CK2α or low molecular weight CK2 inhibitors effectively prevented the progression of renal dysfunction. Based on this background, we focused on developing novel CK2 inhibitors as a therapeutic agent for GN. We have synthesized a series of pyrazine deriva...

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CK2α is essential for embryonic morphogenesis

Cited by 36 publications

References 52 publications

CK2 in Organ Development, Physiology, and Homeostasis

CK2 in Organ Development, Physiology, and Homeostasis

Protein Kinase CK2 and Angiogenesis

The Effects of a Selective CK2 Inhibitor on Anti-glomerular Basement Membrane Glomerulonephritis in Rats

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