MAPK Signaling Pathways in Pancreatic Beta Cells: The Regulation of RAF Activation by Nutrient Stimuli
| dc.contributor.advisor | Cobb, Melanie H. | en |
| dc.creator | Duan, Lingling | en |
| dc.date.accessioned | 2011-02-01T19:32:08Z | |
| dc.date.available | 2011-02-01T19:32:08Z | |
| dc.date.issued | 2011-02-01 | |
| 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.oclc | 719371329 | |
| dc.identifier.uri | https://hdl.handle.net/2152.5/833 | |
| 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 | |
| thesis.degree.department | Graduate School of Biomedical Sciences | en |
| thesis.degree.discipline | Cell Regulation | en |
| thesis.degree.grantor | UT Southwestern Medical Center | en |
| thesis.degree.level | Doctoral | en |
| thesis.degree.name | Doctor of Philosophy | en |
Files
Original bundle
1 - 1 of 1
Loading...
- Name:
- lingling duan MAPK signaling pathways in pancreatic β cells.pdf
- Size:
- 2.03 MB
- Format:
- Adobe Portable Document Format
- Description:
- DIssertation