Functional consequence of PSAT1 association on PKM2's inherent enzymatic activity.

pyruvate kinase;PKM2;PSAT1;phosphoserine aminotransferase 1;enzyme kinetics;protein:protein interaction

Alexis Avidan Vega

University:University of Louisville

Department:Biochemistry and Molecular Biology

关键词: pyruvate kinase;    PKM2;    PSAT1;    phosphoserine aminotransferase 1;    enzyme kinetics;    protein:protein interaction;   

Others  :  https://ir.library.louisville.edu/cgi/viewcontent.cgi?article=4267&context=etd

美国|英语

来源: The Universite of Louisville's Institutional Repository

【 摘 要 】

Pyruvate kinase M2 (PKM2) is predominantly found in tumors, where it allows the cancer cell to adapt to metabolic conditions through allosteric regulation of its activity. We recently discovered that phosphoserine aminotransferase 1 (PSAT1) associates with and activates PKM2. Here, I sought to affirm PSAT1's ability to increase PKM2 activity through kinetic and association studies of wild-type or mutant PKM2 enzymes. I demonstrate that His-tagged WT and mutant PKM2 enzymes are active, exhibit different kinetics, yet cannot be activated by PSAT1. Comparison studies using untagged WT PKM2 suggest that inclusion of the His-tag disrupts PSAT1 association. In support, pull-down strategies failed to demonstrate any PSAT1 interaction with the PKM2 proteins. Future studies should focus on producing the PKM2 variants, potentially in untagged form, to assess their interaction with and activation by PSAT1. These results would add to our understanding of these two crucial proteins that are believed to promote tumor progression.