The M2-type isoenzyme of pyruvate kinase phosphorylates prothymosin et in proliferating lymphocytes

作者：Diaz Jullien Cristina; Moreira David; Sofia Sarandeses Concepcion; Covelo Guillermo; Barbeito Pablo; Freire Manuel^*

来源：Biochimica et Biophysica Acta-Proteins and Proteomics, 2011, 1814(2): 355-365.

DOI：10.1016/j.bbapap.2010.10.004

• Prothymosin
• M2 pyruvate kinase
• Phosphorylation
• Proliferation

Prothymosin alpha (ProT alpha) is a multifunctional protein that, in mammalian cells, is involved in nuclear metabolism through its interaction with histones and that also has a cytosolic role as an apoptotic inhibitor. ProT alpha is phosphorylated by a protein kinase (ProT alpha K), the activity of which is dependent on phosphorylation. ProT alpha phosphorylation also correlates with cell proliferation. Mass spectrometric analysis of ProT alpha K purified from human tumor lymphocytes (NC37 cells) enabled us to identify this enzyme as the M2-type isoenzyme of pyruvate kinase. A study on the relationship between ProT alpha K activity and pyruvate kinase isoforms in NC37 cells and in other cell types confirmed that the M2 isoform is the enzyme responsible for ProT alpha K activity in proliferating cells. Yet, about 10% of the cellular pool of the M2 isoform shows specific affinity for ProT alpha and is responsible for ProT alpha K activity. This pool of M2 protein possesses no observable pyruvate kinase activity and changes its responses to various effectors of pyruvate kinase activity; however, these responses to PK effectors are maintained by the main cellular fraction containing the M2 isoform. Acquisition of ProT alpha K activity by M2 seems to be due to the phosphorylation of serine and threonine residues, which, besides being essential for its catalytic activity, induces a trimeric association of ProT alpha K. This association can be shifted to a tetrameric form by fructose 1, 6-bisphosphate, which results in a decrease in ProT alpha K activity.

• 出版日期2011-2