Tuesday, August 18, 2009

CK II (Casein Kinase II)

Definition
Casein Kinases II is a Ser/Thr protein kinase that has been implicated in cell cycle control, circadian rhythm, DNA repair and other cellular processes1.

Discovery
Casein Kinase II was first purified from rabbit erythrocytes in 19752.

Classification
Casein Kinase II belongs to the Ser/Thr protein kinase family which includes Casein Kinase I as well. The catalytic subunit of casein kinase II has three isoforms, CKII-alpha, alpha’ and alpha” while the regulatory subunit CK II-beta is common to all three catalytic subunits3.

Structural Characteristics
Casein Kinase II is a tetramer with two alpha subunits and two beta subunits. The alpha subunit has an ATP binding pocket3.

Mode of action
Casein Kinase II prefers acidic substrates and phosphorylates proteins with a minimum consensus sequence of Ser-X-X-Acidic, where the acidic residue may be Glu, Asp, pSer or pTyr3.

Functions
Casein Kinase II is widely distributed in various regions of cell and body that reflects its diverse functions. Several 100 substrates of casein kinase II have been identified so far. High levels of Casein Kinase II have been found in several cancers including breast, prostate, lung, head and kidney3. It is required for G1/S and G2/M transitions during cell cycle4. It also phosphorylates proteins involved in DNA repair5. Casein Kinase II promotes cell survival and protects cells from drug induced apoptosis3. Casein kinase 2 activity has been reported to be activated following Wnt signaling pathway activation6.

References
1.Toselli XXP, Russell L and Seldin D (1999). "Globozoospermia in mice lacking the casein kinase II alpha' catalytic subunit". Nature Genetics, 23, 118-121.
2.Kumar R, Tao M (1975). Multiple forms of casein kinase from rabbit erythrocytes. Biochim Biophys Acta, 410(1), 87-98.
3.Litchfield DW (2003). Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. Biochem J, 369 (1), 1-15.
4.Litchfield DW, Lüscher B, Lozeman FJ, Eisenman RN, Krebs EG (1992). Phosphorylation of casein kinase II by p34cdc2 in vitro and at mitosis. J Biol Chem, 267(20), 13943-51.
5.Loizou JI, El-Khamisy SF, Zlatanou A, Moore DJ, Chan DW, Qin J, Sarno S, Meggio F, Pinna LA, Caldecott KW (2004). The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks. Cell, 117(1), 17-28.
6.Gao Y, Wang HY (2006). Casein kinase 2 is activated and essential for Wnt/beta-catenin signaling. J Biol Chem, 281(27), 18394-400.

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