INHIBITION OF PROTEIN KINASE-C-MEDIATED AND CASEIN KINASE-II-MEDIATEDPHOSPHORYLATION OF GAP-43 BY S100-BETA

The effect of the glial-derived protein, S100 beta, on the in vitro ph osphorylation of the growth-associated protein GAP-43 was investigated . S100 beta inhibited in a dose dependent manner the phosphorylation o f GAP-43 by protein kinase C (PKC) or by casein kinase II (CKII). S100 beta appeared to slow down the rate and the degree to which GAP-43 ca n be phosphorylated by either kinase. The specificity of the inhibitio n was demonstrated by the observation that the phosphorylation of two other CKII substrates, casein and a selective peptide substrate, was n ot inhibited by S100 beta. The marked inhibitory effect of S100 beta r equired the presence of calcium in the phosphorylation reactions. In a ddition, S100 beta inhibition of GAP-43 phosphorylation was seen with GAP-43 purified under a variety of conditions that alter acylation, su ggesting that the acylation state of GAP-43 does not affect the abilit y of S100 beta to modulate CKII- or PKC-mediated phosphoryation of GAP -43.