Protein Science, Vol 7, Issue 3 794-798, Copyright © 1998 by Cold Spring Harbor Laboratory Press

FOR THE RECORD

S100B ({beta}{beta}) inhibits the protein kinase C-dependent phosphorylation of a peptide derived from p53 in a Ca(2+)-dependent manner

P. T. WILDER, R. R. RUSTANDI, A. C. DROHAT and D. J. WEBER
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Mayrland 21201

S100B({beta}{beta}) is a dimeric Ca(2+)-binding protein that is known to inhibit the protein kinase C (PKC)-dependent phosphorylation of several proteins. To further characterize this inhibition, we synthesized peptides based on the PKC phosphorylation domains of p53 (residues 367-388), neuromodulin (residues 37-53), and the regulatory domain of PKC (residues 19-31), and tested them as substrates for PKC. All three peptides were shown to be good substrates for the catalytic domain of PKC. As for full-length p53 (Baudier J, Delphin C, Grunwald D, Khochbin S, Lawrence JJ. 1992. Proc Natl Acad Sci USA 89:11627-11631), S100B({beta}{beta}) binds the p53 peptide and inhibits its PKC-dependent phosphorylation (IC(50) = 10 +/- 7 {mu}M) in a Ca(2+)-dependent manner. Similarly, phosphorylation of the neuromodulin peptide and the PKC regulatory domain peptide were inhibited by S100B({beta}{beta}) in the presence of Ca(2+) (IC(50) = 17 +/- 5 {mu}M;IC(50) = 1 +/- 0.5 {mu}M, respectively). At a minimum, the C-terminal EF-hand Ca(2+)-binding domain (residues 61-72) of each S100{beta} subunit must be saturated to inhibit phosphorylation of the p53 peptide as determined by comparing the Ca(2+) dependence of inhibition ((Ca)IC(50) = 29.3 +/- 17.6 {mu}M) to the dissociation of Ca(2+) from the C-terminal EF-hand Ca(2+)-binding domain of S100B({beta}{beta}).
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