Glial-derived S100b protein selectively inhibits recombinant beta protein kinase C (PKC) phosphorylation of neuron-specific protein F1/GAP43

F. S. Sheu, E. C. Azmitia, D. R. Marshak, P. J. Parker, A. Routtenberg

Research output: Contribution to journalArticle

Abstract

Protein F1/GAP43 is neuron-specific, associated with neurite outgrowth during development and a substrate for PKC. This protein is present in high levels in serotonergic neurons which in culture sprout in response to the glial-derived S100b, the beta-beta homodimer. As an initial step in determining whether S100b acts on F1/GAP43 we studied the regulation by S100b of PKC phosphorylation of F1/GAP43. Either the S100b or a mixture of S100a and S100b, both from a brain glial cell source, inhibited in vitro phosphorylation of purified F1/GAP43 by purified PKC in a dose-dependent manner. Using recombinant PKC subtypes, purified S100b preferentially inhibited the F1/GAP43 phosphorylation by the beta subtype. The IC50 of S100b for beta I and beta II PKC was 8 microM while for alpha and gamma PKC it was 64 microM. S100b inhibition was thus subtype-selective. Histone III-S phosphorylation by the four PKC subtypes was not inhibited by S100b. S100b inhibition was thus substrate-selective. Moreover, the effect of S100b on phosphorylation could not be explained by a direct inhibition of kinase activity. Together with earlier studies implicating a role for S100 in synaptic plasticity and neurite outgrowth, the present results suggest that S100b may regulate such functions through its inhibition of neuron-specific PKC substrate (F1/GAP43) phosphorylation. The regulation of this neuron-specific substrate phosphorylation by glial S100 suggests the potential for a novel neuro-glial interaction. Finally, the location of S100 gene on chromosome 21, trisomic in Down's syndrome, and over-expressed in this disorder, as well as in Alzheimer's disease, suggests a link to cognitive impairments in human.
Original languageUndefined
Pages (from-to)62-6
JournalMolecular Brain Research
Volume21
Issue number1-2
Publication statusPublished - 1994

Keywords

  • Animals Brain/*enzymology Calmodulin/pharmacology GAP-43 Protein Isoenzymes/antagonists & inhibitors/isolation & purification Kinetics Male Membrane Glycoproteins/*metabolism Nerve Growth Factors Nerve Tissue Proteins/*metabolism Neuroglia/*physiology Neurons/*metabolism Phosphoproteins/*metabolism Phosphorylation Protein Kinase C/*antagonists & inhibitors/isolation & purification Rats Rats, Sprague-Dawley Recombinant Proteins/antagonists & inhibitors/isolation & purification S100 Calcium Binding Protein beta Subunit S100 Proteins/*pharmacology

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