Mammalian TIMELESS and Protein Kinase G: Partners Linking the Molecular Clockwork to Environmental Light
Barnes, Jessica W.
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https://hdl.handle.net/2142/87928
Description
Title
Mammalian TIMELESS and Protein Kinase G: Partners Linking the Molecular Clockwork to Environmental Light
Author(s)
Barnes, Jessica W.
Issue Date
2004
Doctoral Committee Chair(s)
Gillette, Martha U.
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Cell
Language
eng
Abstract
Research in our lab has determined that GLU activates Protein Kinase G (PKG), and that this activation is required for the mammalian GLU-induced phase advance. Since the Drosophila phase advance proceeds through phosphorylation-dependent degradation of Drosophila TIMELESS (dTIM), I hypothesized that the mammalian light-/GLU-induced phase advance proceeds through PKG-dependent phosphorylation of mammalian TIMELESS (mTIM). In the course of testing this hypothesis, we discovered two isoforms of mTIM, one encoding the full length protein (mTIM-fl) and the other a short splice variant (mTIM-s) corresponding to the last third of mTIM-fl. Only mTIM-fl oscillates in the SCN, associates with other core clock elements, is necessary for circadian rhythmicity, and is degraded by light and GLU in the late night. These findings have contributed to placing mTIM within the core molecular clockwork of mammals, and established both the target of the phase advance signaling pathway and the mechanism by which it is regulated.
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