Research Report Inhibition of protein kinase C- and casein kinase II-mediated phosphorylation of GAP-43 by S100/3

Abstract The effect of the glial-derived protein, $100/3, on the in vitro phosphorylation of the growth-associated protein GAP-43 was investigated. S100/3 inhibited in a dose dependent manner the phosphorylation of GAP-43 by protein kinase C (PKC) or by casein kinase II (CKII). S100/3 appeared to slow down the rate and the degree to which GAP-43 can be phosphorylated by either kinase. The specificity of the inhibition was demonstrated by the observation that the phosphorylation of two other CKII substrates, casein and a selective peptide substrate, was not inhibited by S100/3. The marked inhibitory effect of S100/3 required the presence of calcium in the phosphorylation reactions. In addition, S100/3 inhibition of GAP-43 phosphorylation was seen with GAP-43 purified under a variety of conditions that alter acylation, suggesting that the acylation state of GAP-43 does not affect the ability of S100/3 to modulate CKII- or PKC-mediated phosphoryation of GAP-43. Key words: GAP-43; S-100fl; Casein kinase II; Protein kinase C; Phosphorylation; Calcium; Acylation; Neuromodulin