Csnk1e,Csnk1d phosphorylate Cry and Per proteins

Stable Identifier
Reaction [transition]
Mus musculus
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Csnk1e,Csnk1d phosphorylate Cry and Per proteins

In the cytosol the kinases casein kinase I delta (Csnk1d) and casein kinase I epsilon (Csnk1e) phosphorylate Per1, Per2, Cry1, and Cry2 at multiple sites. Evidence indicates that Per:Cry complexes form a stable ternary complex with either Csnk1e or Csnk1d. Both kinases are able to bind and phosphorylate Per proteins. Csnk1e has been shown to phosphorylate Cry proteins only when they are complexed with Per proteins.
Per proteins contain a nuclear localization sequence and a nuclear export sequence allowing their movement into and out of the nucleus. Phosphorylation is required for transit of Per:Cry:Kinase complexes into the nucleus and for interaction of Per proteins with the ubiquitin-mediated degradation process in the cytoplasm.
Mouse Per2 is phosphoryated at 21 different residues. Phosphorylation at Serine659 (Serine662 in human PER2, which is mutated in one form of familial advanced sleep phase syndrome) causes nuclear retention and stabilization of Per2, however the particular kinase responsible for phosphorylating Serine659 is unknown.

Literature References
PubMed ID Title Journal Year
16983144 Differential effects of PER2 phosphorylation: molecular basis for the human familial advanced sleep phase syndrome (FASPS)

Vanselow, K, Vanselow, JT, Westermark, PO, Reischl, S, Maier, B, Korte, T, Herrmann, A, Herzel, H, Schlosser, A, Kramer, A

Genes Dev 2006
19274088 Interactions between Casein kinase Iepsilon (CKIepsilon) and two substrates from disparate signaling pathways reveal mechanisms for substrate-kinase specificity

Dahlberg, CL, Nguyen, EZ, Goodlett, D, Kimelman, D

PLoS One 2009
17218255 Modeling of a human circadian mutation yields insights into clock regulation by PER2

Xu, Y, Toh, KL, Jones, CR, Shin, JY, Fu, YH, Ptácek, LJ

Cell 2007
15767683 Control of mammalian circadian rhythm by CKIepsilon-regulated proteasome-mediated PER2 degradation

Eide, EJ, Woolf, MF, Kang, H, Woolf, P, Hurst, W, Camacho, F, Vielhaber, EL, Giovanni, A, Virshup, DM

Mol Cell Biol 2005
11779462 Posttranslational mechanisms regulate the mammalian circadian clock

Lee, C, Etchegaray, JP, Cagampang, FR, Loudon, AS, Reppert, SM

Cell 2001
14701732 Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock

Lee, C, Weaver, DR, Reppert, SM

Mol Cell Biol 2004
10848614 Nuclear entry of the circadian regulator mPER1 is controlled by mammalian casein kinase I epsilon

Vielhaber, E, Eide, E, Rivers, A, Gao, ZH, Virshup, DM

Mol Cell Biol 2000
11591712 Nuclear export of mammalian PERIOD proteins

Vielhaber, EL, Duricka, D, Ullman, KS, Virshup, DM

J Biol Chem 2001
10719897 Analysis of clock proteins in mouse SCN demonstrates phylogenetic divergence of the circadian clockwork and resetting mechanisms

Field, MD, Maywood, ES, O'Brien, JA, Weaver, DR, Reppert, SM, Hastings, MH

Neuron 2000
18419299 Reversible protein phosphorylation regulates circadian rhythms

Virshup, DM, Eide, EJ, Forger, DB, Gallego, M, Harnish, EV

Cold Spring Harb Symp Quant Biol 2007
11865049 Control of intracellular dynamics of mammalian period proteins by casein kinase I epsilon (CKIepsilon) and CKIdelta in cultured cells

Akashi, M, Tsuchiya, Y, Yoshino, T, Nishida, E

Mol Cell Biol 2002
11875063 The circadian regulatory proteins BMAL1 and cryptochromes are substrates of casein kinase Iepsilon

Eide, EJ, Vielhaber, EL, Hinz, WA, Virshup, DM

J Biol Chem 2002
15817302 Casein kinase I in the mammalian circadian clock

Eide, EJ, Kang, H, Crapo, S, Gallego, M, Virshup, DM

Methods Enzymol 2005
18400165 Setting clock speed in mammals: the CK1 epsilon tau mutation in mice accelerates circadian pacemakers by selectively destabilizing PERIOD proteins

Meng, QJ, Logunova, L, Maywood, ES, Gallego, M, Lebiecki, J, Brown, TM, Sládek, M, Semikhodskii, AS, Glossop, NR, Piggins, HD, Chesham, JE, Bechtold, DA, Yoo, SH, Takahashi, JS, Virshup, DM, Boot-Handford, RP, Hastings, MH, Loudon, AS

Neuron 2008
19805222 CKIepsilon/delta-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock

Isojima, Y, Nakajima, M, Ukai, H, Fujishima, H, Yamada, RG, Masumoto, KH, Kiuchi, R, Ishida, M, Ukai-Tadenuma, M, Minami, Y, Kito, R, Nakao, K, Kishimoto, W, Yoo, SH, Shimomura, K, Takao, T, Takano, A, Kojima, T, Nagai, K, Sakaki, Y, Takahashi, JS, Ueda, HR

Proc Natl Acad Sci U S A 2009
19948962 Essential roles of CKIdelta and CKIepsilon in the mammalian circadian clock

Lee, H, Chen, R, Lee, Y, Yoo, S, Lee, C

Proc Natl Acad Sci U S A 2009
18786386 Cellular circadian pacemaking and the role of cytosolic rhythms

Hastings, MH, Maywood, ES, O'Neill, JS

Curr Biol 2008
Catalyst Activity
Catalyst Activity
protein serine/threonine kinase activity of Csnk1d,Csnk1e [cytosol]
Physical Entity
Orthologous Events