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THE FUNCTION OF CALCIUM/CALMODULIN DEPENDENT PROTEIN KINASE II IN CELL CYCLE REGULATION

BEAUMAN, SHIRELYN RAE
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1054300335

Abstract Details

2003, PhD, University of Cincinnati, Medicine : Molecular and Cellular Physiology.
Ca 2+ /Calmodulin-dependent protein kinase II (CaMKII) is a multifunctional enzyme that is activated by increases in intracellular Ca 2+ . CaMKII is expressed in all tissues but is most abundant in the brain. Diversity in subunit composition and Ca 2+ sensitivity permit the coordination of multiple cellular functions including muscle contraction, synaptic vesicle release, proliferation and differentiation. The factors allowing CaMKII to mediate a broad spectrum of cellular processes with such precision are just beginning to be understood. Proximity of Ca 2+ signals and the CaMKII activator Calmodulin (CaM), as well as CaMKII subunit composition influence the processes that CaMKII will mediate. As with other kinases, intracellular localization is thought to be a major factor in substrate selection. This dissertation presents two perspectives on CaMKII function. First, in light of the diversity and complexity of CaMKII function, investigation of compartmentalized CaMKII will provide more insight into the physiological condtions under which it operates. Targeted CaMKII genes also have the potential to be therapeutic agents. For example, CaMKII activates a chloride conductance at the plasma membrane of secretory epithelia. Plasma membrane targeted CaMKII may provide stimulation of this chloride channel that is adequate compensation for the defects in fluid secretion characteristic of cystic fibrosis (CF). CF is a lethal hereditary disease characterized by the accumulation of thick mucus secretions from polarized epithelial cells lining the airways and gastrointestinal tract, which impede organ function. The feasibility of targeting CaMKII to specific subcellular locations was investigated in HeLa cells with three CaMKII gene constructs each with a different plasma membrane targeting motif. The data show that plasma membrane targeting of CaMKII is feasible when the targeting motif is attached to the N-terminus of the protein, but not the C-terminus. The second part of this dissertation examines the role of CaMKII at the G2/M transition of the cell cycle. Previous reports show that CaMKII is required for progression from G2 into mitosis. Expression of autonomous CaMKII prevents this transition. Cell lines that display stable expression of an autonomous mutant CaMKII (CaMKIIT286D), reveal experience a delayed mitosis. It is likely that this delay is the result of autonomous CaMKII activation of a cell cycle checkpoint protein that impedes mitosis.
Dr. John R. Dedman (Advisor)
CA 2+ /Calmodulin Dependent Protein Kinase II; Cyclin B1; subcellular localization; cell cycle; Targeting Motifs

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Citations

  • BEAUMAN, S. R. (2003). THE FUNCTION OF CALCIUM/CALMODULIN DEPENDENT PROTEIN KINASE II IN CELL CYCLE REGULATION [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1054300335

    APA Style (7th edition)

  • BEAUMAN, SHIRELYN. THE FUNCTION OF CALCIUM/CALMODULIN DEPENDENT PROTEIN KINASE II IN CELL CYCLE REGULATION. 2003. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1054300335.

    MLA Style (8th edition)

  • BEAUMAN, SHIRELYN. "THE FUNCTION OF CALCIUM/CALMODULIN DEPENDENT PROTEIN KINASE II IN CELL CYCLE REGULATION." Doctoral dissertation, University of Cincinnati, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1054300335

    Chicago Manual of Style (17th edition)

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© 2003, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.