The Experts below are selected from a list of 21 Experts worldwide ranked by ideXlab platform

Lewis T Williams - One of the best experts on this subject based on the ideXlab platform.

  • Casein Kinase Iepsilon in the wnt pathway regulation of beta catenin function
    Proceedings of the National Academy of Sciences of the United States of America, 1999
    Co-Authors: Chie Sakanaka, Peng Leong, Stephen D Harrison, Lewis T Williams
    Abstract:

    Wnt and its intracellular effector β-catenin regulate developmental and oncogenic processes. Using expression cloning to identify novel components of the Wnt pathway, we isolated Casein Kinase Iɛ (CKIɛ). CKIɛ mimicked Wnt in inducing a secondary axis in Xenopus, stabilizing β-catenin, and stimulating gene transcription in cells. Inhibition of endogenous CKIɛ by Kinase-defective CKIɛ or CKIɛ antisense-oligonucleotides attenuated Wnt signaling. CKIɛ was in a complex with axin and other downstream components of the Wnt pathway, including Dishevelled. CKIɛ appears to be a positive regulator of the pathway and a link between upstream signals and the complexes that regulate β-catenin.

David M Virshup - One of the best experts on this subject based on the ideXlab platform.

  • reversible protein phosphorylation regulates circadian rhythms
    Cold Spring Harbor Symposia on Quantitative Biology, 2007
    Co-Authors: David M Virshup, Erik J Eide, Daniel B Forger, Monica Gallego, Vielhaber E Harnish
    Abstract:

    Protein phosphorylation regulates the period of the circadian clock within mammalian cells. Circadian rhythms are an approximately 24-hour cycle that regulates key biological processes. Daily fluctuations of wakefulness, stress hormones, lipid metabolism, immune function, and the cell division cycle are controlled by the molecular clocks that function throughout our bodies. Mutations in regulatory components of the clock can shorten or lengthen the timing of the rhythms and have significant physiological consequences. The clock is formed by a negative feedback loop of transcription, translation, and inhibition of transcription. The precision of clock timing is controlled by protein Kinases and phosphatases. Casein Kinase Iepsilon is a protein Kinase that regulates the circadian clock by periodic phosphorylation of the proteins PER1 and PER2, controlling their stability and localization. The role of phosphorylation in regulating PER function in the clock has been explored in detail. Quantitative modeling has proven to be very useful in making important predictions about how changes in phosphorylation alter the clock's behavior. Quantitative data from biological studies can be used to refine the quantitative model and make additional testable predictions. A detailed understanding of how reversible protein phosphorylation regulates circadian rhythms and a detailed quantitative model that makes clear, testable, and accurate predictions about the clock and how we may manipulate it can have important benefits for human health. Pharmacological manipulation of rhythms could mitigate stress from jet lag, shift work, and perhaps even seasonal affective disorder.

  • the circadian regulatory proteins bmal1 and cryptochromes are substrates of Casein Kinase Iepsilon
    Journal of Biological Chemistry, 2002
    Co-Authors: Erik J Eide, Erica Vielhaber, William A Hinz, David M Virshup
    Abstract:

    Abstract The serine/threonine protein Kinase Casein Kinase I e (CKIe) is a key regulator of metazoan circadian rhythm. Genetic and biochemical data suggest that CKIe binds to and phosphorylates the PERIOD proteins. However, the PERIOD proteins interact with a variety of circadian regulators, suggesting the possibility that CKIe may interact with and phosphorylate additional clock components as well. We find that CRY1 and BMAL1 are phosphoproteins in cultured cells. Mammalian PERIOD proteins act as a scaffold with distinct domains that simultaneously bind CKIe and mCRY1 and mCRY2 (mCRY). mCRY is phosphorylated by CKIe only when both proteins are bound to mammalian PERIOD proteins. BMAL1 is also a substrate for CKIein vitro, and CKIe Kinase activity positively regulates BMAL1-dependent transcription from circadian promoters in reporter assays. We conclude that CKIe phosphorylates multiple circadian substrates and may exert its effects on circadian rhythm in part by a direct effect on BMAL1-dependent transcription.

Erik J Eide - One of the best experts on this subject based on the ideXlab platform.

  • reversible protein phosphorylation regulates circadian rhythms
    Cold Spring Harbor Symposia on Quantitative Biology, 2007
    Co-Authors: David M Virshup, Erik J Eide, Daniel B Forger, Monica Gallego, Vielhaber E Harnish
    Abstract:

    Protein phosphorylation regulates the period of the circadian clock within mammalian cells. Circadian rhythms are an approximately 24-hour cycle that regulates key biological processes. Daily fluctuations of wakefulness, stress hormones, lipid metabolism, immune function, and the cell division cycle are controlled by the molecular clocks that function throughout our bodies. Mutations in regulatory components of the clock can shorten or lengthen the timing of the rhythms and have significant physiological consequences. The clock is formed by a negative feedback loop of transcription, translation, and inhibition of transcription. The precision of clock timing is controlled by protein Kinases and phosphatases. Casein Kinase Iepsilon is a protein Kinase that regulates the circadian clock by periodic phosphorylation of the proteins PER1 and PER2, controlling their stability and localization. The role of phosphorylation in regulating PER function in the clock has been explored in detail. Quantitative modeling has proven to be very useful in making important predictions about how changes in phosphorylation alter the clock's behavior. Quantitative data from biological studies can be used to refine the quantitative model and make additional testable predictions. A detailed understanding of how reversible protein phosphorylation regulates circadian rhythms and a detailed quantitative model that makes clear, testable, and accurate predictions about the clock and how we may manipulate it can have important benefits for human health. Pharmacological manipulation of rhythms could mitigate stress from jet lag, shift work, and perhaps even seasonal affective disorder.

  • the circadian regulatory proteins bmal1 and cryptochromes are substrates of Casein Kinase Iepsilon
    Journal of Biological Chemistry, 2002
    Co-Authors: Erik J Eide, Erica Vielhaber, William A Hinz, David M Virshup
    Abstract:

    Abstract The serine/threonine protein Kinase Casein Kinase I e (CKIe) is a key regulator of metazoan circadian rhythm. Genetic and biochemical data suggest that CKIe binds to and phosphorylates the PERIOD proteins. However, the PERIOD proteins interact with a variety of circadian regulators, suggesting the possibility that CKIe may interact with and phosphorylate additional clock components as well. We find that CRY1 and BMAL1 are phosphoproteins in cultured cells. Mammalian PERIOD proteins act as a scaffold with distinct domains that simultaneously bind CKIe and mCRY1 and mCRY2 (mCRY). mCRY is phosphorylated by CKIe only when both proteins are bound to mammalian PERIOD proteins. BMAL1 is also a substrate for CKIein vitro, and CKIe Kinase activity positively regulates BMAL1-dependent transcription from circadian promoters in reporter assays. We conclude that CKIe phosphorylates multiple circadian substrates and may exert its effects on circadian rhythm in part by a direct effect on BMAL1-dependent transcription.

Chie Sakanaka - One of the best experts on this subject based on the ideXlab platform.

  • Casein Kinase Iepsilon in the wnt pathway regulation of beta catenin function
    Proceedings of the National Academy of Sciences of the United States of America, 1999
    Co-Authors: Chie Sakanaka, Peng Leong, Stephen D Harrison, Lewis T Williams
    Abstract:

    Wnt and its intracellular effector β-catenin regulate developmental and oncogenic processes. Using expression cloning to identify novel components of the Wnt pathway, we isolated Casein Kinase Iɛ (CKIɛ). CKIɛ mimicked Wnt in inducing a secondary axis in Xenopus, stabilizing β-catenin, and stimulating gene transcription in cells. Inhibition of endogenous CKIɛ by Kinase-defective CKIɛ or CKIɛ antisense-oligonucleotides attenuated Wnt signaling. CKIɛ was in a complex with axin and other downstream components of the Wnt pathway, including Dishevelled. CKIɛ appears to be a positive regulator of the pathway and a link between upstream signals and the complexes that regulate β-catenin.

Hitoshi Okamura - One of the best experts on this subject based on the ideXlab platform.

  • constitutive expression and delayed light response of Casein Kinase Iepsilon and idelta mrnas in the mouse suprachiasmatic nucleus
    Journal of Neuroscience Research, 2001
    Co-Authors: Yoshiki Ishida, Kazuhiro Yagita, Tsuyoshi Fukuyama, Masataka Nishimura, Mamoru Nagano, Yasufumi Shigeyoshi, Shun Yamaguchi, Takahide Komori, Hitoshi Okamura
    Abstract:

    Casein Kinase Iepsilon (CKIepsilon) and Casein Kinase Idelta (CKIdelta) phosphorylate clock oscillating mPER proteins, and play a key role in the transcription (post)translation feedback loop that generates circadian rhythm. In the present study, the expression profiles of CKIepsilon and CKIdelta mRNAs were examined in the mice clock center, suprachiasmatic nucleus (SCN). Moderate levels of CKIepsilon and CKIdelta mRNAs were constantly expressed in the SCN in both light:dark and constant dark conditions. This finding supports the hypothesis that CKI may form a constant threshold to the nuclear entry of mPER proteins as in the Drosophila homologue, double-time. Further, we demonstrated that the light exposure at subjective night induced a delayed increase in CKIepsilon and CKIdelta mRNAs in the SCN. CKIepsilon and CKIdelta proteins may play a role on light-induced phase-shift.