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

Fwu Shan Sheu, Efrain C. Azmitia, Daniel R. Marshak, Peter J. Parker, Aryeh Routtenberg

Research output: Contribution to journalArticlepeer-review

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 β-β 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 β subtype. The IC50 of S100b for βI and βII PKC was 8 μM while for α and γ PKC it was 64 μM. 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 languageEnglish (US)
Pages (from-to)62-66
Number of pages5
JournalMolecular Brain Research
Volume21
Issue number1-2
DOIs
StatePublished - Jan 1994

Keywords

  • Alzheimer's disease
  • Down's syndrome
  • Glial S100b
  • Protein F1/GAP43
  • Protein kinase C
  • Synaptic plasticity

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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