Inhibition of protein kinase C- and casein kinase II-mediated phosphorylation of GAP-43 by S100 beta.
The effect of the glial-derived protein, S100 beta, on the in vitro phosphorylation of the growth-associated protein GAP-43 was investigated. S100 beta inhibited in a dose dependent manner the phosphorylation of 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 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 beta. The marked inhibitory effect of S100 beta required the presence of calcium in the phosphorylation reactions. In addition, S100 beta 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 beta to modulate CKII- or PKC-mediated phosphorylation of GAP-43.
Lin
L H
LH
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Van Eldik
L J
LJ
Osheroff
N
N
Norden
J J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D047390:Casein Kinase II; D019922:GAP-43 Protein; D006133:Growth Substances / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000494:pharmacology*
D019922:GAP-43 Protein; D006133:Growth Substances; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D009418:S100 Proteins; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C