SAICAR induces protein kinase activity of PKM2 that is necessary for sustained proliferative signaling of cancer cells
| Autor: | Zainab M. Doctor, Young-Sam Lee, Kirstie E. Keller, Zachary W. Dwyer |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Thyroid Hormones
Mitogen-Activated Protein Kinase 3 Protein Array Analysis Mitogen-activated protein kinase kinase Ligands MAP2K7 Xenopus laevis Cell Line Tumor Animals Humans ASK1 Phosphorylation Molecular Biology Protein kinase B Protein Kinase Inhibitors Cell Proliferation Cell Nucleus biology MAP kinase kinase kinase Cyclin-dependent kinase 4 Cyclin-dependent kinase 2 Membrane Proteins Cell Biology Ribonucleotides Aminoimidazole Carboxamide Recombinant Proteins Cell biology Adenosine Diphosphate Gene Expression Regulation Neoplastic Isoenzymes biology.protein Carrier Proteins HeLa Cells Protein Binding Signal Transduction |
| Zdroj: | Molecular cell. 53(5) |
| ISSN: | 1097-4164 |
| Popis: | Abnormal metabolism and sustained proliferation are hallmarks of cancer. Pyruvate kinase M2 (PKM2) is a metabolic enzyme that plays important roles in both processes. Recently, PKM2 was shown to have protein kinase activity phosphorylating histone H3 and promoting cancer cell proliferation. However, the mechanism and extent of this protein kinase in cancer cells remain unclear. Here, we report that binding of succinyl-5-aminoimidazole-4-carboxamide-1-ribose-5′-phosphate (SAICAR), a metabolite abundant in proliferating cells, induces PKM2’s protein kinase activity in vitro and in cells. Protein microarray experiments revealed that more than 100 human proteins, mostly protein kinases, are phosphorylated by PKM2-SAICAR. In particular, PKM2-SAICAR phosphorylates and activates Erk1/2, which in turn sensitizes PKM2 for SAICAR binding through phosphorylation. Additionally, PKM2-SAICAR was necessary to induce sustained Erk1/2 activation and mitogen-induced cell proliferation. Thus, the ligand-induced protein kinase activity from PKM2 is a mechanism that directly couples cell proliferation with intracellular metabolic status. |
| Databáze: | OpenAIRE |
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