| Abstract | 第1-9页 |
| 中文摘要 | 第9-11页 |
| Abbreviations | 第11-13页 |
| Chapter 1 A Brief Review about CKl Family and Evolution of Gene Duplication | 第13-54页 |
| Introduction | 第13-14页 |
| 1. CK1 evoltuion | 第14-29页 |
| ·Gene family evolution and gene duplication | 第16-25页 |
| ·Gene duplication | 第16-21页 |
| ·Orthologue and paralogue | 第21-25页 |
| ·Evolution of CK1 family | 第25-29页 |
| 2. Functions of CKl1family members | 第29-35页 |
| ·Participation of CKlin multiple pathways | 第29-33页 |
| ·Function of CK1 in cell growth and cell division | 第29-30页 |
| ·Participation of CK1 in the Wnt and Hedgehog pathways | 第30-32页 |
| ·Involvement of CK1 in neurodegeneration | 第32-33页 |
| ·Phosphorylation targets of CKls | 第33-35页 |
| 3. CK1 and circadian clock | 第35-44页 |
| ·Brief introduction of circadian clock | 第36-39页 |
| ·Role of CK1 in circadian clock | 第39-41页 |
| ·Circadian clock related diseases | 第41-44页 |
| References | 第44-54页 |
| Chapter 2 Functional Variation between DBT and CK1δ/ε on SR Motif in Drosophila | 第54-71页 |
| 1. Material and methods | 第54-61页 |
| ·Drosophila culture | 第54页 |
| ·Fly locomotor activity analysis | 第54-55页 |
| ·Transgenic fly generation | 第55-59页 |
| ·Plasmid preparation for transgenic fly | 第55-57页 |
| ·Transgenic fly injection | 第57-58页 |
| ·Establishment of transgenic lines | 第58-59页 |
| ·Establishment of hPER2 and CK1 double transgenic flies | 第59页 |
| ·Protein detection | 第59-61页 |
| ·Collection of fly heads | 第59页 |
| ·Western blotting | 第59-61页 |
| ·Sequence alignment | 第61页 |
| 2. Results | 第61-69页 |
| ·Mutants on hPER2 SR motif do not show different circadian phenotypesin Drosophila | 第61-64页 |
| ·CK1δ but not DBT is able to show different circadian function onhPER2~(S662) hPER2~(S662D) and hPER2~(S662G) flies | 第64-66页 |
| ·Different modifications on hPER2 mutants by CK18 but not DBT | 第66-67页 |
| ·Similar functional effect of DBT and CK1δ on drosophila PER | 第67-68页 |
| ·Similar functional effect of CK1δ and CK1ε on hPER2 | 第68-69页 |
| 3. Discussion | 第69-71页 |
| Chapter 3 Identify the Sequence Responsible for DBT and CK1δ Functional Divergence on the SR Motif | 第71-87页 |
| 1. Material and methods | 第71-73页 |
| ·Plasmid Construction | 第71-72页 |
| ·Cell culture and transfection | 第72页 |
| ·Western blotting | 第72页 |
| ·In vitro kinase assay | 第72-73页 |
| 2. Results | 第73-85页 |
| ·CK18-DBT(5) fragment is responsible for the kinase activity difference betweenDBT and CK1δ | 第73-76页 |
| ·Verify the functions of CK1δ-D(5) and CK1δ-D(3) fragments in Drosophila | 第76-79页 |
| ·In vitro kinase assay for the functions of DBT, CK1δ and CK1δ-D(5)fragment | 第79-80页 |
| ·Structural basis for the functional variance between DBT and CK1δ | 第80-82页 |
| ·CK1δ/ε-D(5)sequence conservation is in consistent with CK1δ/ε enzyme activityon SR motif | 第82-85页 |
| 3. Discussion | 第85-87页 |
| Chapter 4 Emergence of Conserved SR Motif in the Vertebrates | 第87-94页 |
| 1. Material and methods | 第87页 |
| 2. Results | 第87-94页 |
| ·Conservation of SR motif in CKδ/ε substrates is correlated with the Kinase activityof CK1δ/ε | 第87-90页 |
| ·Conservation of SR motif is correlated with the substrate interactionswith CK1δ/ε | 第90页 |
| ·High conservation of putative SR motif in vertebrates | 第90-94页 |
| Discussion | 第94-99页 |
| References | 第99-109页 |
| 致谢 | 第109-111页 |
| Publications | 第111-112页 |
| 附件 | 第112-113页 |
