Purification of protein phosphatase 4 catalytic subunit: inhibition by the antitumour drug fostriecin and other tumour suppressors and promoters

Protein phosphatase 4 (PP4) is a protein serine/ threonine phosphatase that predominantly localises to centrosomes and plays a role in microtubule organisation at centrosomes. Here, PP4 catalytic subunit has been purified from porcine testis to near homogeneity and a specific activity of 680 mU/mg against phosphorylase a. The antitumour drug, fostriecin, inhibits PP4 catalytic subunit (IC50 3 nM) with similar potency to PP2A catalytic subunit (IC50 1.5 nM), PP4 is also inhibited in the nanomolar range by several naturally occurring tumour promoters and toxins, with similar IC50 values to those obtained for PP2A, The gene for human PP4 catalytic subunit localises to 16p11.2. (C) 1998 Federation of European Biochemical Societies.