MAPK Signaling Pathways in Pancreatic Beta Cells: The Regulation of RAF Activation by Nutrient Stimuli
| dc.contributor.advisor | Cobb, Melanie | en |
| dc.creator | Duan, Lingling | en |
| dc.date.accessioned | 2011-02-01T19:32:08Z | en |
| dc.date.accessioned | 2014-02-19T22:02:46Z | |
| dc.date.available | 2011-02-01T19:32:08Z | en |
| dc.date.available | 2014-02-19T22:02:46Z | |
| dc.date.issued | 2011-02-01T19:32:08Z | en |
| dc.description.abstract | In pancreatic β cells cells, ERK1 and ERK2 participate in nutrient sensing and their activities rise and fall as a function of glucose concentration over the physiologic range. Glucose metabolism triggers calcium influx and release of calcium from intracellular stores which are required for ERK1/2 activity. Calcium influx also activates the calcium-dependent phosphatase calcineurin, which is required for maximal ERK1/2 activation by glucose. Calcineurin controls insulin gene expression by ERK1/2-dependent and -independent mechanisms. This study showed that in β cells, glucose activates the ERK1/2 cascade primarily through B-Raf. Glucose also enhances dimerization of B-Raf with C-Raf. Furthermore, calcineurin up-regulates B-Raf activity and stabilizes C-Raf/B-Raf in response to glucose. Calcineurin binds to B-Raf in both unstimulated and stimulated cells. B-Raf phospho-T401 is one of the target sites that can be dephosphorylated by calcineurin. This study reveals that cross-talk between Raf and calcineurin is essential for the maximal activation of ERK1/2 in the glucose signaling pathways. [Keywords: TCF; POP-1; Wnt; embryogenesis; C. elegans] | en |
| dc.identifier | 719371329 | en |
| dc.identifier.uri | http://hdl.handle.net/2152.5/833 | en |
| dc.language.iso | en | en |
| dc.subject | Mitogen-Activated Protein Kinase 1 | en |
| dc.subject | Insulin-Secreting Cells | en |
| dc.subject | Calcineurin | en |
| dc.subject | Glucose | en |
| dc.title | MAPK Signaling Pathways in Pancreatic Beta Cells: The Regulation of RAF Activation by Nutrient Stimuli | en |
| dc.type | Thesis | en |
| thesis.date.available | 2013-01-26 | en |
| thesis.degree.discipline | Cell Regulation | en |
| thesis.degree.grantor | Graduate School of Biomedical Sciences | en |
| thesis.degree.level | Ph.D. | en |