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Casein kinase 1

The Casein kinase 1 family (EC of protein kinases are serine/threonine-selective enzymes that function as regulators of signal transduction pathways in most eukaryotic cell types.



By the early 1950s it was known from metabolic labeling studies using radioactive phosphate that the phosphate of phosphoproteins inside cells can sometimes undergo rapid exchange of new phosphate for old. In order to perform experiments that would allow isolation and characterization of the enzymes involved in attaching and removing phosphate from proteins, there was a need for convenient substrates for protein kinases and protein phosphatases. Casein has been used as a substrate since the earliest days of research on protein phosphorylation [1]. By the late 1960s, cyclic AMP-dependent protein kinase had been purified and most attention was centered on kinases and phosphatases that could regulate the activity of important enzymes. Casein kinase activity associated with the endoplasmic reticulum of mammary glands was first characterized in 1974 and its activity was shown to not depend on cyclic AMP [2].

casein kinase 1, alpha 1
Symbol(s) CSNK1A1
Entrez 1452
OMIM 600505


Casein kinase activity was found to be present in most cell types and to be associated with multiple enzymes. The type 1 casein kinase family of related gene products are now given designations such as "casein kinase 1 alpha" and "casein kinase 1 epsilon". Casein kinase 1 alpha has been suggested to play a role in phosphorylation of Disheveled in the Wnt signaling pathway [3].

casein kinase 1, gamma 1
Symbol(s) CSNK1G1
Entrez 53944
OMIM 606274
casein kinase 1, gamma 2
Symbol(s) CSNK1G2
Entrez 1455
OMIM 602214
casein kinase 1, gamma 3
Symbol(s) CSNK1G3
Entrez 1456
OMIM 604253

In humans there are three casein kinase 1 gamma enzymes. Working with the Xenopus system, Davidson et al screened for proteins that can regulate the Wnt signaling pathway by interacting with the Wnt receptor LRP[4]. They reported that Xenopus casein kinase 1 gamma (CK1gamma) is associated with the cell membrane and binds to LRP. CK1gamma was found to be needed for Wnt signaling through LRP. is both necessary and sufficient to transduce LRP6 signalling in vertebrates and Drosophila cells. Wnt binding to LRP causes a rapid increase in phosphorylation of the cytoplasmic domain of LRP by CK1gamma. Davidson et al proposed that phosphorylation of LRP6 by CK1gamma promotes binding of Axin to LRP and activation of the Wnt signaling pathway[4].

casein kinase 1, epsilon
Symbol(s) CSNK1E
Entrez 1454
OMIM 600863

Casein kinase 1 epsilon is also important in the Wnt signaling pathway [5] and the Hedgehog signaling pathway [6].

Casein kinase 1 epsilon also acts in a molecular pathway that regulates the circadian rhythm [7].

See also


  1. ^ G. Burnett and E. Kennedy (1954) "The enzymatic phosphorylation of proteins" in Journal of Biological Chemistry Volume 211, pages 969-980. Entrez PubMed 13221602
  2. ^ E. Bingham and H. Farrel (1974) "Casein kinase from the Golgi apparatus of lactating mammary gland" in Journal of Biological Chemistry Volume 249, pages 3647-3651. Entrez PubMed 4364664
  3. ^ R. Takada, H. Hijikata, H. Kondoh and S. Takada (2005) "Analysis of combinatorial effects of Wnts and Frizzleds on beta-catenin/armadillo stabilization and Dishevelled phosphorylation" in Genes Cells Volume 10, pages 919-928. Entrez PubMed 16115200.
  4. ^ a b 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" in Nature Volume 438, pages 867-872. Entrez PubMed 16341016
  5. ^ Wojciech Swiatek, I-Chun Tsai, Laura Klimowski, Andrea Pepler, Janet Barnette, H. Joseph Yost and David M. Virshup (2004) "Regulation of casein kinase I epsilon activity by Wnt signaling" in Journal of Biological Chemistry Volume 279, pages 13011-13017. Entrez PubMed 14722104
  6. ^ L. Lum and P. A. Beachy (2004) "The Hedgehog response network: sensors, switches, and routers" in Science Volume 304, pages 1755-1759 Entrez PubMed 15205520
  7. ^ Erik J. Eide, Margaret F. Woolf, Heeseog Kang, Peter Woolf, William Hurst, Fernando Camacho, Erica L. Vielhaber, Andrew Giovanni and David M. Virshup (2005) "Control of mammalian circadian rhythm by CKIepsilon-regulated proteasome-mediated PER2 degradation" in Molecular and Cellular Biology Volume 25, pages 2795-2807. Entrez PubMed 15767683
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Casein_kinase_1". A list of authors is available in Wikipedia.
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