MLK3 phophorylates AMPK independently of LKB1.
Emerging evidence has shown that cellular energy metabolism is regulated by the AMPK and MLK3-JNK signaling pathways, but the functional link between them remains to be determined. The present study aimed to explore the crosstalk between MLK3 and AMPK. We found that both JNK and AMPK were phosphoryl...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4395454?pdf=render |
| _version_ | 1811211869335060480 |
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| author | Lingyu Luo Shanshan Jiang Deqiang Huang Nonghua Lu Zhijun Luo |
| author_facet | Lingyu Luo Shanshan Jiang Deqiang Huang Nonghua Lu Zhijun Luo |
| author_sort | Lingyu Luo |
| collection | DOAJ |
| description | Emerging evidence has shown that cellular energy metabolism is regulated by the AMPK and MLK3-JNK signaling pathways, but the functional link between them remains to be determined. The present study aimed to explore the crosstalk between MLK3 and AMPK. We found that both JNK and AMPK were phosphorylated at their activation sites by TNF-α, Anisomycin, H2O2 and sorbitol. Interestingly, sorbitol stimulated phosphorylation of AMPK at T172 in LKB1-deficient cells. Following the screening of more than 100 kinases, we identified that MLK3 induced phosphorylation of AMPK at T172. Our in vitro analysis further revealed that MLK3-mediated phosphorylation of AMPK at T172 was independent of AMP, but addition of AMP caused a mobility shift of AMPK, an indication of autophosphorylation, suggesting that AMP binding and phosphorylation of T172 leads to maximal activation of AMPK. GST-pull down assays showed a direct interaction between AMPKα1 subunit and MLK3. Altogether, our results indicate that MLK3 serves as a common upstream kinase of AMPK and JNK and functions as a direct upstream kinase for AMPK independent of LKB1. |
| first_indexed | 2024-04-12T05:19:42Z |
| format | Article |
| id | doaj.art-dde71b4d36c34fd98fcd57a615a9eabc |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T05:19:42Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-dde71b4d36c34fd98fcd57a615a9eabc2022-12-22T03:46:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01104e012392710.1371/journal.pone.0123927MLK3 phophorylates AMPK independently of LKB1.Lingyu LuoShanshan JiangDeqiang HuangNonghua LuZhijun LuoEmerging evidence has shown that cellular energy metabolism is regulated by the AMPK and MLK3-JNK signaling pathways, but the functional link between them remains to be determined. The present study aimed to explore the crosstalk between MLK3 and AMPK. We found that both JNK and AMPK were phosphorylated at their activation sites by TNF-α, Anisomycin, H2O2 and sorbitol. Interestingly, sorbitol stimulated phosphorylation of AMPK at T172 in LKB1-deficient cells. Following the screening of more than 100 kinases, we identified that MLK3 induced phosphorylation of AMPK at T172. Our in vitro analysis further revealed that MLK3-mediated phosphorylation of AMPK at T172 was independent of AMP, but addition of AMP caused a mobility shift of AMPK, an indication of autophosphorylation, suggesting that AMP binding and phosphorylation of T172 leads to maximal activation of AMPK. GST-pull down assays showed a direct interaction between AMPKα1 subunit and MLK3. Altogether, our results indicate that MLK3 serves as a common upstream kinase of AMPK and JNK and functions as a direct upstream kinase for AMPK independent of LKB1.http://europepmc.org/articles/PMC4395454?pdf=render |
| spellingShingle | Lingyu Luo Shanshan Jiang Deqiang Huang Nonghua Lu Zhijun Luo MLK3 phophorylates AMPK independently of LKB1. PLoS ONE |
| title | MLK3 phophorylates AMPK independently of LKB1. |
| title_full | MLK3 phophorylates AMPK independently of LKB1. |
| title_fullStr | MLK3 phophorylates AMPK independently of LKB1. |
| title_full_unstemmed | MLK3 phophorylates AMPK independently of LKB1. |
| title_short | MLK3 phophorylates AMPK independently of LKB1. |
| title_sort | mlk3 phophorylates ampk independently of lkb1 |
| url | http://europepmc.org/articles/PMC4395454?pdf=render |
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