Title | STE20 phosphorylation of AMPK-related kinases revealed by biochemical purifications combined with genetics |
Authors | Liu, Yuxiang Wang, Tao, V Cui, Yunfeng Li, Chaoyi Jiang, Lifen Rao, Yi |
Affiliation | Peking Univ, Coll Chem & Chem Engn, Peking Tsinghua Ctr Life Sci,Sch Life Sci,Sch Pha, Hlth Sci Ctr,Lab Neurochem Biol,Dept Chem Biol,PK, Beijing, Peoples R China Chinese Inst Brain Res, Beijing, Peoples R China Capital Med Univ, Sch Basic Med Sci, Beijing, Peoples R China Changping Lab, Beijing, Peoples R China Shenzhen Bay Lab, Inst Mol Physiol, Shenzhen, Guangdong, Peoples R China |
Keywords | ACTIVATED PROTEIN-KINASE UPSTREAM KINASE LKB1 BETA PAK1 SNF1 AUTOPHOSPHORYLATION HOMEOSTASIS PATHWAY TARGET |
Issue Date | May-2022 |
Publisher | JOURNAL OF BIOLOGICAL CHEMISTRY |
Abstract | We have recently purified mammalian sterile 20 (STE20)- like kinase 3 (MST3) as a kinase for the multifunctional kinases, AMP-activated protein kinase-related kinases (ARKs). However, unresolved questions from this study, such as remaining phosphorylation activities following deletion of the Mst3 gene from human embryonic kidney cells and mice, led us to conclude that there were additional kinases for ARKs. Further purification recovered Ca2+/calmodulin-dependent protein kinase kinases 1 and 2 (CaMKK1 and 2), and a third round of purification revealed mitogen-activated protein kinase kinase kinase kinase 5 (MAP4K5) as potential kinases of ARKs. We then demonstrated that MST3 and MAP4K5, both belonging to the STE20-like kinase family, could phosphorylate all 14 ARKs both in vivo and in vitro. Further examination of all 28 STE20 kinases detected variable phosphorylation activity on AMP-activated protein kinase (AMPK) and the salt-inducible kinase 3 (SIK3). Taken together, our results have revealed novel relationships between STE20 kinases and ARKs, with potential physiological and pathological implications. |
URI | http://hdl.handle.net/20.500.11897/648387 |
DOI | 10.1016/j.jbc.2022.101928 |
Indexed | SCI(E) |
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