Definition
Casein Kinase I (CKI) is a Ser/Thr protein kinase family that has been implicated in regulation of signal transduction1.
Discovery
Casein Kinase activity associated with the endoplasmic reticulum of mammary glands was first characterized in 19742.
Classification
CK I belongs to the kinase family of proteins. It has five isoforms- alpha, beta, gamma, delta and epsilon which are conserved from yeast to humans3.
Structural Characteristics
CK I structure is characterized by nine alpha helices and nine beta strands. The N terminal and C terminal lobes are connected by a single loop4. The cleft lying between the two lobes binds to the nucleotide substrate4. The small N-terminal lobe contains five twisted antiparallel strands, one helix, and the glycine rich sequence motif, Glyl9-Glu-Gly-Ser-Phe-Gly-Val25. The C terminal lobe consists of four long alpha helices in a antiparallel bundle with a fifth long helix almost perpendicular to the bundle. Overall CK I is rich in Lys and Arg residues4.
Mode of action
Previously phosphorylated substrates are good candidates for secondary phosphorylation by CK I5. It also prefers acidic substrates5.
Functions
CK I is involved in membrane trafficking, circadian rhythm, cell cycle progression, chromosome segregation, apoptosis and cellular differentiation3. Mutations and deregulation of CK1 expression and activity has been linked to various diseases such as Alzheimer's, Parkinson's disease, sleeping disorders and cancer3. It is also involved in Wnt signaling pathway6.
References
1. Gross SD, Anderson RA (1998). Casein kinase I: spatial organization and positioning of a multifunctional protein kinase family. Cell Signal, 10(10), 699-711.
2. Bingham E and Farrel H (1974). Casein kinase from the Golgi apparatus of lactating mammary gland. J. Biol. Chem., 249, 3647-51.
3. Knippschild U, Wolff S, Giamas G, Brockschmidt C, Wittau M, Würl PU, Eismann T, Stöter M (2005). The role of the casein kinase 1 (CK1) family in different signaling pathways linked to cancer development. Onkologie, 28(10), 508-14.
4. Xu RM, Carmel G,Sweet RM, Kuret J and Cheng X (1995). Crystal structure of casein kinase-1, a phosphate-directed protein kinase. EMBO J, 14 (5), 1015-23.
5. Flotow H, Graves PR, Wang AQ, Fiol CJ, Roeske RW, Roach PJ (1990). Phosphate groups as substrate determinants for casein kinase I action. J Biol Chem, 265(24), 14264-9.
6. G. Davidson, W. Wu, J. Shen, J. Bilic, U. Fenger, P. Stannek, A. Glinka and C. Niehrs (2005). Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction. Nature, 438, 867-872.