Journal article
Inhibition of AMP Kinase by the Protein Phosphatase 2A Heterotrimer, PP2A(Ppp2r2d)
The Journal of biological chemistry, v 290(17), pp 10588-10598
24 Apr 2015
PMID: 25694423
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
AMP kinase is a heterotrimeric serine/threonine protein kinase that regulates a number of metabolic processes, including lipid biosynthesis and metabolism. AMP kinase activity is regulated by phosphorylation, and the kinases involved have been uncovered. The particular phosphatases counteracting these kinases remain elusive. Here we discovered that the protein phosphatase 2A heterotrimer, PP2A(Ppp2r2d), regulates the phosphorylation state of AMP kinase by dephosphorylating Thr-172, a residue that activates kinase activity when phosphorylated. Co-immunoprecipitation and co-localization studies indicated that PP2A(Ppp2r2d) directly interacted with AMP kinase. PP2A(Ppp2r2d) dephosphorylated Thr-172 in rat aortic and human vascular smooth muscle cells. A positive correlation existed between decreased phosphorylation, decreased acetyl-CoA carboxylase Acc1 phosphorylation, and sterol response element-binding protein 1c-dependent gene expression. PP2APpp2r2d protein expression was up-regulated in the aortas of mice fed a high fat diet, and the increased expression correlated with increased blood lipid levels. Finally, we found that the aortas of mice fed a high fat diet had decreased AMP kinase Thr-172 phosphorylation, and contained an Ampk-PP2A(Ppp2r2d) complex. Thus, PP2A(Ppp2r2d) may antagonize the aortic AMP kinase activity necessary for maintaining normal aortic lipid metabolism. Inhibiting PP2A(Ppp2r2d) or activating AMP kinase represents a potential pharmacological treatment for many lipid-related diseases.
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Details
- Title
- Inhibition of AMP Kinase by the Protein Phosphatase 2A Heterotrimer, PP2A(Ppp2r2d)
- Creators
- Biny K. Joseph - Inst Metab Disorders, Hamilton, NJ 08691 USAHsing-Yin Liu - Inst Metab Disorders, Hamilton, NJ 08691 USAJamie Francisco - Inst Metab Disorders, Hamilton, NJ 08691 USADevanshi Pandya - Inst Metab Disorders, Hamilton, NJ 08691 USAMelissa Donigan - Inst Metab Disorders, Hamilton, NJ 08691 USAChristina Gallo-Ebert - Inst Metab Disorders, Hamilton, NJ 08691 USACaroline Giordano - AnsysAdam Bata - AnsysJoseph T. Nickels - Inst Metab Disorders, Hamilton, NJ 08691 USA
- Publication Details
- The Journal of biological chemistry, v 290(17), pp 10588-10598
- Publisher
- Elsevier
- Number of pages
- 11
- Grant note
- Genesis Biotechnology Group
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000353404500002
- Scopus ID
- 2-s2.0-84928406936
- Other Identifier
- 991021229998604721
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- Web of Science research areas
- Biochemistry & Molecular Biology