ERK2-Pyruvate Kinase Axis Permits Phorbol 12-Myristate 13-Acetate-induced Megakaryocyte Differentiation in K562 Cells
| Autor: | Rameshwar N. K. Bamezai, Prakasam Gopinath, Farid Ahmad Siddiqui, Mohammad Askandar Iqbal, Noor Chaman |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
MAP Kinase Signaling System
Megakaryocyte differentiation Cellular differentiation Pyruvate Kinase Biology PKM2 Biochemistry chemistry.chemical_compound Humans Glycolysis Molecular Biology Mitogen-Activated Protein Kinase 1 Cell Cycle Integrin beta3 Cell Differentiation Cell Biology Cell biology Metabolism chemistry Tetradecanoylphorbol Acetate Carcinogens Phorbol K562 Cells Megakaryocytes Pyruvate kinase K562 cells |
| Zdroj: | Journal of Biological Chemistry. 290:23803-23815 |
| ISSN: | 0021-9258 |
| Popis: | Metabolic changes that contribute to differentiation are not well understood. Overwhelming evidence shows the critical role of glycolytic enzyme pyruvate kinase (PK) in directing metabolism of proliferating cells. However, its role in metabolism of differentiating cells is unclear. Here we studied the role of PK in phorbol 12-myristate 13-acetate (PMA)-induced megakaryocytic differentiation in human leukemia K562 cells. We observed that PMA treatment decreased cancer-type anabolic metabolism but increased ATP production, along with up-regulated expression of two PK isoforms (PKM2 and PKR) in an ERK2-dependent manner. Interestingly, silencing of PK (PKM2 and PKR) inhibited PMA-induced megakaryocytic differentiation, as revealed by decreased expression of megakaryocytic differentiation marker CD61 and cell cycle behavior. Further, PMA-induced ATP production reduced greatly upon PK silencing, suggesting that PK is required for ATP synthesis. In addition to metabolic effects, PMA treatment also translocated PKM2, but not PKR, into nucleus. ERK1/2 knockdowns independently and together suggested the role of ERK2 in the up-regulation of both the isoforms of PK, proposing a role of ERK2-PK isoform axis in differentiation. Collectively, our findings unravel ERK2 guided PK-dependent metabolic changes during PMA induction, which are important in megakaryocytic differentiation. |
| Databáze: | OpenAIRE |
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