Chemical genetic screen for novel AMPKalpha2 substrates reveals a role for AMPK in regulating a network of proteins involved in mitosis, cytokinesis and cytoskeletal reorganization
Abstract/Contents
- Abstract
- The ability to adapt to nutrient deprivation is a key characteristic of all organisms. The energy-sensing AMP-activated protein kinase (AMPK) is activated by low nutrient levels. Functions of AMPK, other than its role in cellular metabolism, are just beginning to emerge. For the study presented in this thesis, I used a chemical genetics screen to identify direct substrates of AMPK in human cells. I found that AMPK phosphorylates 28 novel substrates, several of which are involved in mitosis, cytokinesis, and cytoskeletal rearrangements. I identified the residues phosphorylated by AMPK in vivo in several substrates, including protein phosphatase 1 regulatory subunit 12C (PPP1R12C) and p21-activated protein kinase (PAK2). Activation or inhibition of AMPK activity is sufficient to disrupt the proper completion of cytokinesis and results in the formation of multinucleated cells. Furthermore, AMPK-induced phosphorylation is necessary for PPP1R12C interaction with 14-3-3[lowercase Zeta], phosphorylation of myosin regulatory light chain, and mitotic progression of human cells. These findings suggest that AMPK coordinates nutrient status with mitosis completion, which may be critical for the organism's response to low nutrients during development, or in adult stem and cancer cells.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Banko, Max Ryan | |
|---|---|---|
| Associated with | Stanford University, Department of Genetics | |
| Primary advisor | Brunet, Anne, 1972- | |
| Thesis advisor | Brunet, Anne, 1972- | |
| Thesis advisor | Ferrell, James Ellsworth | |
| Thesis advisor | Kim, Stuart | |
| Thesis advisor | Pringle, John | |
| Advisor | Ferrell, James Ellsworth | |
| Advisor | Kim, Stuart | |
| Advisor | Pringle, John |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Max Banko. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Ph.D. Stanford University 2011 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Max Ryan Banko
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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