Challenges and Reinterpretation of Antibody-Based Research on Phosphorylation of Tyr307 on PP2Ac.

Cell Reports
Sahar MazharGoutham Narla

Abstract

Aberrant hyperphosphorylation of the protein phosphatase 2A catalytic subunit (PP2Ac) at Tyr307 has been associated with aggressive disease and poor clinical outcome in multiple cancers. However, the study of reversible phosphorylation at this site has relied entirely upon the use of antibodies-most prominently, the clone E155. Here, we provide evidence that the E155 and F-8 phospho-Tyr307 antibodies cannot differentiate between phosphorylated and unphosphorylated forms of PP2Ac. The form of PP2Ac bound by these antibodies in H358 cells is unphosphorylated at the C-terminal tail. Furthermore, these antibodies are sensitive to additional protein modifications that occur near Tyr307, including Thr304 phosphorylation and Leu309 methylation, when these post-translational modifications are present. Thus, studies that used these antibodies to report PP2Ac hyperphosphorylation require reinterpretation, as these antibodies cannot be reliably used as readouts for a single PP2Ac post-translational modification (PTM) change.

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Citations

Jun 6, 2020·Essays in Biochemistry·Dimitriya H Garvanska, Jakob Nilsson
Oct 31, 2020·Biochemical Society Transactions·Isha Nasa, Arminja N Kettenbach
Jun 27, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Mohammad Golam SabbirPeter Zahradka

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