A truncated isoform of the PP2A B56 subunit promotes cell motility through paxillin phosphorylation

Both F10 and BL6 sublines of B16 mouse melanoma cells are metastatic after intravenous injection, but only BL6 cells are metastatic after subcutaneous injection, Retrotransposon insertion was found to produce an N-terminally truncated form (Delta gamma 1) of the B56 gamma 1 regulatory subunit isoform of protein phosphatase (PP) 2A in BL6 cells, but not in F10 cells, We found an interaction of paxillin with PP2A C and B56 gamma subunits by co-immunoprecipitation. B56 gamma 1 co-localized with paxillin at focal adhesions, suggesting a role for this isoform in targeting PP2A to paxillin, In this regard, Delta gamma 1 behaved similarly to B56 gamma 1. However, the Delta gamma 1-containing PP2A heterotrimer was insufficient for the dephosphorylation of paxillin. Transfection with Delta gamma 1 enhanced paxillin phosphorylation on serine residues and recruitment into focal adhesions, and cell spreading with an actin network. In addition, Delta gamma 1 rendered F10 cells as highly metastatic as BL6 cells. These results suggest that mutations in PP2A regulatory subunits may cause malignant progression.