Kinase Family CK2

Kinase Classification: Group CMGC: Family CK2

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CK2 (formerly known as Casein Kinase 2) is found in all eukaryotes and is known for having a very large number of substrates and its role in circadian rhythms

Evolution

CK2 is found in all eukaryotes examined, usually in one or two copies (CK2a1 and CK2a2 in human, also known as CSNK2A1 and CSNK2A2. CK2 also has a beta (b) subunit, and usually forms a tetramer of either or both of the two catalytic subunits and two beta subunits (a1,a2,b,b or a1, a1, b, b or a2, a2, b, b).

Two copies of CK2a are found in yeast, vertebrates, Selaginella and Dictyostelium. These appear to be independent duplications and may be encouraged by the tetrameric structure. Yeast also has two beta subunits.

Domain Structure

Almost all CK2 consist of a kinase domain flanked by short non-domain sequences.

Catalytic Activity

Recently it has been shown that CK2 α-subunits undergo intermolecular tyrosine-autophosphorylation at Y182, which may represent a specific regulatory mechanism. Also, CK2 is able to phosphorylate, under special circumstances, tyrosyl residues in proteins. CK2 is implicated in a variety of cellular functions (1,2).

History

CK2 was the first protein kinase to be described, by Burnett and Kennedy in 1954 [1] (http://www.jbc.org/content/211/2/969.full.pdf). Both CK1 and CK2 were named casein kinases due to the use of casein as an assay substrate, but they are not believed to be casein-specific (hence the term CK2, or the acronym redefinition as "Cell Kinase 2").

Function

CK2 is believed to be constitutively active, phosphorylating on largely acidic sites. In human has a reported >300 substrates [2]. Accordingly, it has been implicated in a wide array of functions. Many of these substrates are signaling proteins and 60 are transcription factors

Drosophila CK2a has been implicated in Hh signaling, aggregates, circadian, dpp/NFkB, PAK, trnascription, neuronal wiring,

CK2 is little-studied in C. elegans, though it has been shown to interact with fibroblast growth factor (FGF) [3] which corroborates the interaction of human FGF1 and FGF2 with CK2 complexes [1, 2, 3, 4, 4, 5, 6, 7, 7, 8, 8, 8, 8, 9, 10, 11, 12]