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

Fwu Shan Sheu, Efrain Azmitia, Daniel R. Marshak, Peter J. Parker, Aryeh 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 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 - 1994

Fingerprint

GAP-43 Protein
Recombinant Proteins
Neuroglia
Protein Kinase C
Phosphorylation
Neurons
Proteins
Serotonergic Neurons
Chromosomes, Human, Pair 21
Neuronal Plasticity
Down Syndrome
Histones
Inhibitory Concentration 50
Alzheimer Disease
Phosphotransferases
Inhibition (Psychology)
Brain

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

Cite this

Glial-derived S100b protein selectively inhibits recombinant β protein kinase C (PKC) phosphorylation of neuron-specific protein F1/GAP43. / Sheu, Fwu Shan; Azmitia, Efrain; Marshak, Daniel R.; Parker, Peter J.; Routtenberg, Aryeh.

In: Molecular Brain Research, Vol. 21, No. 1-2, 1994, p. 62-66.

Research output: Contribution to journalArticle

Sheu, Fwu Shan ; Azmitia, Efrain ; Marshak, Daniel R. ; Parker, Peter J. ; Routtenberg, Aryeh. / Glial-derived S100b protein selectively inhibits recombinant β protein kinase C (PKC) phosphorylation of neuron-specific protein F1/GAP43. In: Molecular Brain Research. 1994 ; Vol. 21, No. 1-2. pp. 62-66.
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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.",
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T1 - Glial-derived S100b protein selectively inhibits recombinant β protein kinase C (PKC) phosphorylation of neuron-specific protein F1/GAP43

AU - Sheu, Fwu Shan

AU - Azmitia, Efrain

AU - Marshak, Daniel R.

AU - Parker, Peter J.

AU - Routtenberg, Aryeh

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N2 - 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.

AB - 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.

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