Structural highlights
Function
[KC1E_HUMAN] Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates DVL1. Central component of the circadian clock. In balance with PP1, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phospohorylation. Controls PER1 and PER2 nuclear transport and degradation. Inhibits cytokine-induced granuloytic differentiation.[1] [2] [3] [4]
Publication Abstract from PubMed
Casein kinase 1 epsilon (CK1epsilon) and its closest homologue CK1delta are key regulators of diverse cellular processes. We report two crystal structures of PF4800567, a potent and selective inhibitor of CK1epsilon, bound to the kinase domains of human CK1epsilon and CK1delta as well as one apo CK1epsilon crystal structure. These structures provide a molecular basis for the strong and specific inhibitor interactions with CK1epsilon and suggest clues for further development of CK1delta inhibitors.
Structural Basis for the Potent and Selective Inhibition of Casein Kinase 1 Epsilon.,Long AM, Zhao H, Huang X J Med Chem. 2012 Nov 9. PMID:23106386[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hino S, Michiue T, Asashima M, Kikuchi A. Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is essential for Wnt-3a-induced accumulation of beta-catenin. J Biol Chem. 2003 Apr 18;278(16):14066-73. Epub 2003 Jan 28. PMID:12556519 doi:http://dx.doi.org/10.1074/jbc.M213265200
- ↑ Okamura A, Iwata N, Nagata A, Tamekane A, Shimoyama M, Gomyo H, Yakushijin K, Urahama N, Hamaguchi M, Fukui C, Chihara K, Ito M, Matsui T. Involvement of casein kinase Iepsilon in cytokine-induced granulocytic differentiation. Blood. 2004 Apr 15;103(8):2997-3004. Epub 2004 Jan 8. PMID:15070676 doi:http://dx.doi.org/10.1182/blood-2003-08-2768
- ↑ Shirogane T, Jin J, Ang XL, Harper JW. SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein. J Biol Chem. 2005 Jul 22;280(29):26863-72. Epub 2005 May 24. PMID:15917222 doi:http://dx.doi.org/10.1074/jbc.M502862200
- ↑ Partch CL, Shields KF, Thompson CL, Selby CP, Sancar A. Posttranslational regulation of the mammalian circadian clock by cryptochrome and protein phosphatase 5. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10467-72. Epub 2006 Jun 21. PMID:16790549 doi:http://dx.doi.org/10.1073/pnas.0604138103
- ↑ Long AM, Zhao H, Huang X. Structural Basis for the Potent and Selective Inhibition of Casein Kinase 1 Epsilon. J Med Chem. 2012 Nov 9. PMID:23106386 doi:http://dx.doi.org/10.1021/jm301336n
