A proteomics analysis of CK2β(-/-) C2C12 cells provides novel insights into the biological functions of the non-catalytic β subunit

FEBS J. 2019 Apr;286(8):1561-1575. doi: 10.1111/febs.14799. Epub 2019 Mar 18.

Abstract

The acronym CK2 (derived from the misnomer 'casein kinase-2') denotes a pleiotropic acidophilic protein kinase implicated in a plethora of cellular functions, whose abnormally high expression correlates with malignancy. CK2 holoenzyme is composed of two catalytic (α and/or α') and two noncatalytic β-subunits. The β-subunits are not responsible for either activation or inactivation of the catalytic ones. Hence, to gain additional information about the roles of the individual CK2 subunits, we have generated C2C12 myoblasts entirely devoid either of both catalytic subunits, or of the β-subunit. Here, we show that while CK2α/α'(-/-) cells grow similarly to wild-type cells, the growth of CK2β(-/-) cells is severely impaired, consistent with the hypothesis that not all cellular functions of the β-subunit are mediated by CK2 holoenzyme. To get a deeper insight into the functional implications of the β-subunit, a quantitative proteomics study of CK2β(-/-) cells was performed, leading to the identification and quantification of more than 1200 proteins. Of these, 187 showed a significantly altered expression (fold change ≥ 1.5 or ≤ -1.5) as compared to wild-type cells. A functional analysis of these proteins discloses the implication of CK2β in many processes, for example, cell cycle, proliferation, transport, metabolic processes, etc., and in some of which the catalytic subunits of CK2 do not seem to play a relevant role. On the other hand, the pool of ecto-CK2 is not apparently affected by the lack of the β-subunit. Collectively, our data corroborate the concept that the cellular functions of the β-subunit of CK2 are partially independent of CK2 holoenzyme.

Keywords: cell signaling; protein kinases; protein phosphorylation; quantitative proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism*
  • Catalytic Domain
  • Cell Line
  • Cell Proliferation
  • Gene Knockout Techniques
  • Mice
  • Myoblasts / metabolism*
  • Protein Subunits
  • Proteomics / methods*
  • Tandem Mass Spectrometry

Substances

  • Protein Subunits
  • Casein Kinase II