Susceptibility of the prion protein to enzymic phosphorylation

Ten protein kinases have been assayed for their ability to phosphorylate in vitro the recombinant bovine PrP (25-242) (rbPrP). Substantial phosphoryla tion was observed with PKC, CK2, and two tyrosine kinases, Lyn and c-Fgr. W ith regard to CK2, phosphorylation occurs at Ser 154 with a stoichiometry o f about 0.1 mol phosphate/mol rbPrP, which is doubled by mild heat treatmen t of rbPrP. Heat also reduces the overall protein ellipticity, suggesting t hat reversibly unfolded conformers are more susceptible to phosphorylation. Our data disclose the possibility that phosphorylation might modulate PrP biological activity. (C) 2000 Academic Press.